Differential effects of cannabis extracts and pure plant cannabinoids on hippocampal neurones and glia.

PubMed

Ryan, Duncan; Drysdale, Alison J; Pertwee, Roger G; Platt, Bettina

2006-11-20

We have shown previously that the plant cannabinoid cannabidiol (CBD) elevates intracellular calcium levels in both cultured hippocampal neurones and glia. Here, we investigated whether the main psychotropic constituent of cannabis, Delta(9)-tetrahydrocannabinol (THC) alone or in combination with other cannabis constituents can cause similar responses, and whether THC affects the responses induced by CBD. Our experiments were performed with 1 microM pure THC (pTHC), with 1 microM pure CBD (pCBD), with a high-THC, low CBD cannabis extract (eTHC), with a high-CBD, low THC cannabis extract (eCBD), with a mixture of eTHC and eCBD (THC:CBD=1:1) or with corresponding 'mock extracts' that contained only pTHC and pCBD mixed in the same proportion as in eTHC, eCBD or the 1:1 mixture of eTHC and eCBD. We detected significant differences in neurones both between the effects of pTHC and eTHC and between the effects of pCBD and eCBD. There were also differences between the Ca(2+) responses evoked in both neurones and glia by eTHC and mock eTHC, but not between eCBD and mock eCBD. A particularly striking observation was the much increased response size and maximal responder rates induced by the mixture of eTHC and eCBD than by the corresponding 1:1 mixture of pTHC and pCBD. Our data suggest that THC shares the ability of CBD to elevate Ca(2+) levels in neurones and glia, that THC and CBD interact synergistically and that the cannabis extracts have other constituents yet to be identified that can significantly modulate the ability of THC and CBD to raise Ca(2+) levels.

Ultrasound-Assisted Extraction of Cannabinoids from Cannabis Sativa L. Optimized by Response Surface Methodology.

PubMed

Agarwal, Charu; Máthé, Katalin; Hofmann, Tamás; Csóka, Levente

2018-03-01

Ultrasonication was used to extract bioactive compounds from Cannabis sativa L. such as polyphenols, flavonoids, and cannabinoids. The influence of 3 independent factors (time, input power, and methanol concentration) was evaluated on the extraction of total phenols (TPC), flavonoids (TF), ferric reducing ability of plasma (FRAP) and the overall yield. A face-centered central composite design was used for statistical modelling of the response data, followed by regression and analysis of variance in order to determine the significance of the model and factors. Both the solvent composition and the time significantly affected the extraction while the sonication power had no significant impact on the responses. The response predictions obtained at optimum extraction conditions of 15 min time, 130 W power, and 80% methanol were 314.822 mg GAE/g DW of TPC, 28.173 mg QE/g DW of TF, 18.79 mM AAE/g DW of FRAP, and 10.86% of yield. A good correlation was observed between the predicted and experimental values of the responses, which validated the mathematical model. On comparing the ultrasonic process with the control extraction, noticeably higher values were obtained for each of the responses. Additionally, ultrasound considerably improved the extraction of cannabinoids present in Cannabis. Low frequency ultrasound was employed to extract bioactive compounds from the inflorescence part of Cannabis. The responses evaluated were-total phenols, flavonoids, ferric reducing assay and yield. The solvent composition and time significantly influenced the extraction process. Appreciably higher extraction of cannabinoids was achieved on sonication against control. © 2018 Institute of Food Technologists®.

Effects of acute oral Delta9-tetrahydrocannabinol and standardized cannabis extract on the auditory P300 event-related potential in healthy volunteers.

PubMed

Roser, Patrik; Juckel, Georg; Rentzsch, Johannes; Nadulski, Thomas; Gallinat, Jürgen; Stadelmann, Andreas M

2008-08-01

Reduced amplitudes of auditory evoked P300 are a robust finding in schizophrenic patients, indicating deficient attentional resource allocation and active working memory. Delta9-Tetrahydrocannabinol (Delta9-THC), the main active constituent of Cannabis sativa, has been known to acutely impair cognitive abilities in several domains, particularly in memory and attention. Given the psychotic-like effects of Delta9-THC, a cannabinoid hypothesis of schizophrenia has been proposed. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on P300 amplitude in 20 healthy volunteers (age 28.2+/-3.1 years, 10 male) by comparing Delta9-THC and standardized cannabis extract containing Delta9-THC and cannabidiol (CBD). P300 waves were recorded during a choice reaction task. As expected, Delta9-THC revealed a significant reduction of P300 amplitude at midline frontal, central, and parietal electrodes. CBD has been known to abolish many of the psychotropic effects of Delta9-THC, but, unexpectedly, failed to demonstrate a reversal of Delta9-THC-induced P300 reduction. Moreover, there were no correlations between cannabinoid plasma concentrations and P300 parameters. These data suggest that Delta(9)-THC may lead to acute impairment of attentional functioning and working memory. It can be speculated whether the lack of effect of CBD may be due to an insufficient dose used or to an involvement of neurotransmitter systems in P300 generation which are not influenced by CBD.

Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress.

PubMed

Comelli, Francesca; Bettoni, Isabella; Colleoni, Mariapia; Giagnoni, Gabriella; Costa, Barbara

2009-12-01

Neuropathy is the most common complication of diabetes and it is still considered to be relatively refractory to most of the analgesics. The aim of the present study was to explore the antinociceptive effect of a controlled cannabis extract (eCBD) in attenuating diabetic neuropathic pain. Repeated treatment with cannabis extract significantly relieved mechanical allodynia and restored the physiological thermal pain perception in streptozotocin (STZ)-induced diabetic rats without affecting hyperglycemia. In addition, the results showed that eCBD increased the reduced glutathione (GSH) content in the liver leading to a restoration of the defence mechanism and significantly decreased the liver lipid peroxidation suggesting that eCBD provides protection against oxidative damage in STZ-induced diabetes that also strongly contributes to the development of neuropathy. Finally, the nerve growth factor content in the sciatic nerve of diabetic rats was restored to normal following the repeated treatment with eCBD, suggesting that the extract was able to prevent the nerve damage caused by the reduced support of this neurotrophin. These findings highlighted the beneficial effects of cannabis extract treatment in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and a specific action upon nerve growth factor. Copyright (c) 2009 John Wiley & Sons, Ltd.

Acute psychotropic effects of oral cannabis extract with a defined content of Delta9-tetrahydrocannabinol (THC) in healthy volunteers.

PubMed

Kaufmann, R M; Kraft, B; Frey, R; Winkler, D; Weiszenbichler, S; Bäcker, C; Kasper, S; Kress, H G

2010-01-01

The medical use of cannabinoids is limited mainly by their undesirable effects. With respect to acute psychotropic effects, the aim of this study is the comparison of an oral cannabis extract and low-dose diazepam in a cross-over experiment in drug-naïve healthy women. Sixteen healthy females participated in this randomized, double-blind, active comparator-controlled, single-dose, balanced 2-way cross-over study. Cannabis extract with standardised Delta (9)-tetrahydrocannabinol (THC) content (20 mg) or active placebo (5 mg diazepam) was administered orally. Subjects were assessed by self- and observer-rated visual analogue scales (VAS), the BRIEF PSYCHIATRIC RATING SCALE (BPRS) and three psychomotor tests up to 6 h after administration. VAS showed significantly elevated fatigue, drowsiness, dizziness, and "feeling high" after cannabis as compared to baseline and diazepam. BPRS scores were significantly higher after cannabis intake. Only in one psychomotor test a decrease of psychomotor activity after cannabis was evident. One subject in the cannabis condition experienced severe transient psychotic symptoms. Orally administered cannabis produced significant central depressant side-effects compared to diazepam, mostly subjective effects (VAS) but marginal effects in psychomotor performance in 15 healthy females. Regarding the medical use of cannabis, a rigorous benefit-risk analysis and an exact psychiatric assessment before and during treatment are necessary. (c) Georg Thieme Verlag KG Stuttgart . New York.

Determination of Acid and Neutral Cannabinoids in Extracts of Different Strains of Cannabis sativa Using GC-FID.

PubMed

Ibrahim, Elsayed A; Gul, Waseem; Gul, Shahbaz W; Stamper, Brandon J; Hadad, Ghada M; Abdel Salam, Randa A; Ibrahim, Amany K; Ahmed, Safwat A; Chandra, Suman; Lata, Hemant; Radwan, Mohamed M; ElSohly, Mahmoud A

2018-03-01

Cannabis ( Cannabis sativa L.) is an annual herbaceous plant that belongs to the family Cannabaceae. Trans -Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD) are the two major phytocannabinoids accounting for over 40% of the cannabis plant extracts, depending on the variety. At the University of Mississippi, different strains of C. sativa, with different concentration ratios of CBD and Δ 9 -THC, have been tissue cultured via micropropagation and cultivated. A GC-FID method has been developed and validated for the qualitative and quantitative analysis of acid and neutral cannabinoids in C. sativa extracts. The method involves trimethyl silyl derivatization of the extracts. These cannabinoids include tetrahydrocannabivarian, CBD, cannabichromene, trans -Δ 8 -tetrahydrocannabinol, Δ 9 -THC, cannabigerol, cannabinol, cannabidiolic acid, cannabigerolic acid, and Δ 9 -tetrahydrocannabinolic acid-A. The concentration-response relationship of the method indicated a linear relationship between the concentration and peak area ratio with R 2  > 0.999 for all 10 cannabinoids. The precision and accuracy of the method were found to be ≤ 15% and ± 5%, respectively. The limit of detection range was 0.11 - 0.19 µg/mL, and the limit of quantitation was 0.34 - 0.56 µg/mL for all 10 cannabinoids. The developed method is simple, sensitive, reproducible, and suitable for the detection and quantitation of acidic and neutral cannabinoids in different extracts of cannabis varieties. The method was applied to the analysis of these cannabinoids in different parts of the micropropagated cannabis plants (buds, leaves, roots, and stems). Georg Thieme Verlag KG Stuttgart · New York.

Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Vaney, C; Heinzel-Gutenbrunner, M; Jobin, P; Tschopp, F; Gattlen, B; Hagen, U; Schnelle, M; Reif, M

2004-08-01

Cannabis may alleviate some symptoms associated with multiple sclerosis (MS). This study investigated the effect of an orally administered standardized Cannabis sativa plant extract in MS patients with poorly controlled spasticity. During their inpatient rehabilitation programme, 57 patients were enrolled in a prospective, randomized, double-blind, placebo-controlled crossover study of cannabis-extract capsules standardized to 2.5 mg tetrahydrocannabinol (THC) and 0.9 mg cannabidiol (CBD) each. Patients in group A started with a drug escalation phase from 15 to maximally 30 mg THC by 5 mg per day if well tolerated, being on active medication for 14 days before starting placebo. Patients in group B started with placebo for seven days, crossed to the active period (14 days) and closed with a three-day placebo period (active drug dose escalation and placebo sham escalation as in group A). Measures used included daily self-report of spasm frequency and symptoms, Ashworth Scale, Rivermead Mobility Index, 10-m timed walk, nine-hole peg test, paced auditory serial addition test (PASAT), and the digit span test. In the 50 patients included into the intention-to-treat analysis set, there were no statistically significant differences associated with active treatment compared to placebo, but trends in favour of active treatment were seen for spasm frequency, mobility and getting to sleep. In the 37 patients (per-protocol set) who received at least 90% of their prescribed dose, improvements in spasm frequency (P = 0.013) and mobility after excluding a patient who fell and stopped walking were seen (P = 0.01). Minor adverse events were slightly more frequent and severe during active treatment, and toxicity symptoms, which were generally mild, were more pronounced in the active phase. A standardized Cannabis sativa plant extract might lower spasm frequency and increase mobility with tolerable side effects in MS patients with persistent spasticity not responding to other drugs.

Species-specific susceptibility to cannabis-induced convulsions.

PubMed

Whalley, Benjamin J; Lin, Hong; Bell, Lynne; Hill, Thomas; Patel, Amesha; Gray, Roy A; Elizabeth Roberts, C; Devinsky, Orrin; Bazelot, Michael; Williams, Claire M; Stephens, Gary J

2018-02-19

Numerous claims are made for cannabis' therapeutic utility upon human seizures, but concerns persist about risks. A potential confounder is the presence of both Δ 9 -tetrahydrocannabinol (THC), variously reported to be pro- and anticonvulsant, and cannabidiol (CBD), widely confirmed as anticonvulsant. Therefore, we investigated effects of prolonged exposure to different THC/CBD cannabis extracts on seizure activity and associated measures of endocannabinoid (eCB) system signalling. Cannabis extract effects on in vivo neurological and behavioural responses, and on bioanalyte levels, were measured in rats and dogs. Extract effects on seizure activity were measured using electroencephalography telemetry in rats. eCB signalling was also investigated using radioligand binding in cannabis extract-treated rats and treatment-naïve rat, mouse, chicken, dog and human tissue. Prolonged exposure to cannabis extracts caused spontaneous, generalized seizures, subserved by epileptiform discharges in rats, but not dogs, and produced higher THC, but lower 11-hydroxy-THC (11-OH-THC) and CBD, plasma concentrations in rats versus dogs. In the same rats, prolonged exposure to cannabis also impaired cannabinoid type 1 receptor (CB 1 receptor)-mediated signalling. Profiling CB 1 receptor expression, basal activity, extent of activation and sensitivity to THC suggested interspecies differences in eCB signalling, being more pronounced in a species that exhibited cannabis extract-induced seizures (rat) than one that did not (dog). Sustained cannabis extract treatment caused differential seizure, behavioural and bioanalyte levels between rats and dogs. Supporting radioligand binding data suggest species differences in eCB signalling. Interspecies variations may have important implications for predicting cannabis-induced convulsions from animal models. © 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

A cannabigerol-rich Cannabis sativa extract, devoid of [INCREMENT]9-tetrahydrocannabinol, elicits hyperphagia in rats.

PubMed

Brierley, Daniel I; Samuels, James; Duncan, Marnie; Whalley, Benjamin J; Williams, Claire M

2017-06-01

Nonpsychoactive phytocannabinoids (pCBs) from Cannabis sativa may represent novel therapeutic options for cachexia because of their pleiotropic pharmacological activities, including appetite stimulation. We have recently shown that purified cannabigerol (CBG) is a novel appetite stimulant in rats. As standardized extracts from Cannabis chemotypes dominant in one pCB [botanical drug substances (BDSs)] often show greater efficacy and/or potency than purified pCBs, we investigated the effects of a CBG-rich BDS, devoid of psychoactive [INCREMENT]-tetrahydrocannabinol, on feeding behaviour. Following a 2 h prefeed satiation procedure, 16 male Lister-hooded rats were administered CBG-BDS (at 30-240 mg/kg) or vehicle. Food intake, meal pattern microstructure and locomotor activity were recorded over 2 h. The total food intake was increased by 120 and 240 mg/kg CBG-BDS (1.53 and 1.36 g, respectively, vs. 0.56 g in vehicle-treated animals). Latency to feeding onset was dose dependently decreased at all doses, and 120 and 240 mg/kg doses increased both the number of meals consumed and the cumulative size of the first two meals. No significant effect was observed on ambulatory activity or rearing behaviour. CBG-BDS is a novel appetite stimulant, which may have greater potency than purified CBG, despite the absence of [INCREMENT]-tetrahydrocannabinol in the extract.

Evaluation of a reduced nicotine product standard: moderating effects of and impact on cannabis use*

PubMed Central

Pacek, Lauren R.; Vandrey, Ryan; Dermody, Sarah S.; Denlinger, Rachel L.; Lemieux, Andrine; Tidey, Jennifer W.; McClernon, F. Joseph; Bangdiwala, Ananta S.; Drobes, David J.; al'Absi, Mustafa; Strasser, Andrew A.; Koopmeiners, Joseph S.; Hatsukami, Dorothy K.; Donny, Eric C.

2016-01-01

Introduction The Family Smoking Prevention and Tobacco Control Act authorized the FDA to reduce the nicotine content in cigarettes. Research is needed to guide proposed regulations, including evaluation of consequences to public health. This study evaluated how a reduced nicotine product standard might be moderated by and impact cannabis use. Methods Secondary analysis of a controlled clinical trial examining the effects of nicotine content in cigarettes in adult daily smokers. Linear regression assessed whether baseline cannabis use moderated behavioral, subjective, or physiological effects of smoking very low nicotine content (VLNC) versus normal nicotine content (NNC) cigarettes. Repeated measures analysis of associations between nicotine condition and prevalence and frequency of cannabis use was completed using generalized estimating equations (GEE). Results Among cannabis users and non-users, smokers randomized to VLNC cigarettes reported lower nicotine dependence, cigarettes per day, biomarkers of nicotine exposure, and craving compared to smokers randomized to NNC cigarettes. Non-cannabis using smokers randomized to VLNC cigarettes also reported lower smoking dependence motives and had lower tobacco-specific nitrosamine exposure and total puff volume versus smokers randomized to NNC cigarettes. For cannabis users, smokers randomized to VLNC cigarettes reported decreased positive affect. Cannabis use did not moderate most effects of VLNC cigarettes. VLNC cigarette use did not impact the prevalence or frequency of cannabis use. Discussion Findings provide evidence that nicotine reduction in cigarettes could have beneficial effects on cigarette smoking regardless of cannabis use. Results suggest that transitioning to VLNC cigarettes is unlikely to alter current rates of cannabis use. PMID:27590743

Evaluation of a reduced nicotine product standard: Moderating effects of and impact on cannabis use.

PubMed

Pacek, Lauren R; Vandrey, Ryan; Dermody, Sarah S; Denlinger-Apte, Rachel L; Lemieux, Andrine; Tidey, Jennifer W; McClernon, F Joseph; Bangdiwala, Ananta S; Drobes, David J; al'Absi, Mustafa; Strasser, Andrew A; Koopmeiners, Joseph S; Hatsukami, Dorothy K; Donny, Eric C

2016-10-01

The Family Smoking Prevention and Tobacco Control Act authorized the FDA to reduce the nicotine content in cigarettes. Research is needed to guide proposed regulations, including evaluation of consequences to public health. This study evaluated how a reduced nicotine product standard might be moderated by and impact cannabis use. Secondary analysis of a controlled clinical trial examining the effects of nicotine content in cigarettes in adult daily smokers. Linear regression assessed whether baseline cannabis use moderated behavioral, subjective, or physiological effects of smoking very low nicotine content (VLNC) versus normal nicotine content (NNC) cigarettes. Repeated measures analysis of associations between nicotine condition and prevalence and frequency of cannabis use was completed using generalized estimating equations (GEE). Cannabis use did not moderate most of the following effects of VLNC cigarettes: Among cannabis users and non-users, smokers randomized to VLNC cigarettes reported lower nicotine dependence, cigarettes per day, biomarkers of nicotine exposure, and craving compared to smokers randomized to NNC cigarettes. Non-cannabis using smokers randomized to VLNC cigarettes also reported lower smoking dependence motives and had lower tobacco-specific nitrosamine exposure and total puff volume versus smokers randomized to NNC cigarettes. For cannabis users, smokers randomized to VLNC cigarettes reported decreased positive affect. VLNC cigarette use did not impact the prevalence or frequency of cannabis use. Findings provide evidence that nicotine reduction in cigarettes could have beneficial effects on cigarette smoking regardless of cannabis use. Results suggest that transitioning to VLNC cigarettes is unlikely to alter current rates of cannabis use. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[A novel analgesics made from Cannabis].

PubMed

Szendrei, Kálmán

2004-01-20

Bayer AG has recently announced that it acquired exclusive rights for the marketing of GW Pharmaceuticals' new medicine Sativex in Europe and in other regions. Sativex is a sublingual spray on Cannabis extract basis, and is equipped with an electronic tool to facilitate accurate dosing and to prevent misuses. It is standardized for the THC and CBD. The new analgesic is proposed for the treatment of muscle spasticity and pains accompanying multiple sclerosis and as an efficient analgetic for neurogenic pain not responding well to opioids and to other therapies available. The entirely new mechanism of action through the recently discovered cannabinoid receptor system may offer a real therapeutic potential to the drug. Although the Government of Netherlands has authorized the sale of pharmaceutical grade Cannabis herb by pharmacies in the Netherlands, the availability on the pharmaceutical market of the registered preparation may render requests for the authorization of the smoking of Cannabis herb (marihuana) by individuals suffering of multiple sclerosis, neurogenic pain, AIDS wasting syndrome unnecessary. Nevertheless, the "old chameleon" plant Cannabis appears to gradually regain its previous status in mainstream therapy and pharmacy. As long as the plant Cannabis and its products continue to be classified as narcotic drugs, medical use of the new preparation will need close supervision.

Biological effects of THC and a lipophilic cannabis extract on normal and insulin resistant 3T3-L1 adipocytes.

PubMed

Gallant, M; Odei-Addo, F; Frost, C L; Levendal, R-A

2009-10-01

Type 2 diabetes, a chronic disease, affects about 150 million people world wide. It is characterized by insulin resistance of peripheral tissues such as liver, skeletal muscle, and fat. Insulin resistance is associated with elevated levels of tumor necrosis factor alpha (TNF-alpha), which in turn inhibits insulin receptor tyrosine kinase autophosphorylation. It has been reported that cannabis is used in the treatment of diabetes. A few reports indicate that smoking cannabis can lower blood glucose in diabetics. Delta(9)-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis. This study aimed to determine the effect of a lipophilic cannabis extract on adipogenesis, using 3T3-L1 cells, and to measure its effect on insulin sensitivity in insulin resistant adipocytes. Cells were cultured in Dulbecco's modified eagle medium (DMEM) with 10% fetal bovine serum (FBS) and differentiated over a 3 day period for all studies. In the adipogenesis studies, differentiated cells were exposed to the extract in the presence and absence of insulin. Lipid content and glucose uptake was subsequently measured. Insulin-induced glucose uptake increased, while the rate of adipogenesis decreased with increasing THC concentration. Insulin-resistance was induced using TNF-alpha, exposed to the extract and insulin-induced glucose uptake measured. Insulin-induced glucose was increased in these cells after exposure to the extract. Semiquantitative real time polymerase chain reaction (RT-PCR) was performed after ribonucleic acid (RNA) extraction to evaluate the effects of the extract on glucose transporter isotype 4 (GLUT-4), insulin receptor substrate-1 (IRS-1) and IRS-2 gene expression.

Heat exposure of Cannabis sativa extracts affects the pharmacokinetic and metabolic profile in healthy male subjects.

PubMed

Eichler, Martin; Spinedi, Luca; Unfer-Grauwiler, Sandra; Bodmer, Michael; Surber, Christian; Luedi, Markus; Drewe, Juergen

2012-05-01

The most important psychoactive constituent of CANNABIS SATIVA L. is Δ (9)-tetrahydrocannabinol (THC). Cannabidiol (CBD), another important constituent, is able to modulate the distinct unwanted psychotropic effect of THC. In natural plant extracts of C. SATIVA, large amounts of THC and CBD appear in the form of THCA-A (THC-acid-A) and CBDA (cannabidiolic acid), which can be transformed to THC and CBD by heating. Previous reports of medicinal use of cannabis or cannabis preparations with higher CBD/THC ratios and use in its natural, unheated form have demonstrated that pharmacological effects were often accompanied with a lower rate of adverse effects. Therefore, in the present study, the pharmacokinetics and metabolic profiles of two different C. SATIVA extracts (heated and unheated) with a CBD/THC ratio > 1 were compared to synthetic THC (dronabinol) in a double-blind, randomized, single center, three-period cross-over study involving 9 healthy male volunteers. The pharmacokinetics of the cannabinoids was highly variable. The metabolic pattern was significantly different after administration of the different forms: the heated extract showed a lower median THC plasma AUC (24 h) than the unheated extract of 2.84 vs. 6.59 pmol h/mL, respectively. The later was slightly higher than that of dronabinol (4.58 pmol h/mL). On the other hand, the median sum of the metabolites (THC, 11-OH-THC, THC-COOH, CBN) plasma AUC (24 h) was higher for the heated than for the unheated extract. The median CBD plasma AUC (24 h) was almost 2-fold higher for the unheated than for the heated extract. These results indicate that use of unheated extracts may lead to a beneficial change in metabolic pattern and possibly better tolerability. © Georg Thieme Verlag KG Stuttgart · New York.

Tasty THC: Promises and Challenges of Cannabis Edibles.

PubMed

Barrus, Daniel G; Capogrossi, Kristen L; Cates, Sheryl C; Gourdet, Camille K; Peiper, Nicholas C; Novak, Scott P; Lefever, Timothy W; Wiley, Jenny L

2016-11-01

Food products containing cannabis extract (edibles) have emerged as a popular and lucrative facet of the legalized market for both recreational and medicinal cannabis. The many formulations of cannabis extracts used in edibles present a unique regulatory challenge for policy makers. Though edibles are often considered a safe, discreet, and effective means of attaining the therapeutic and/or intoxicating effects of cannabis without exposure to the potentially harmful risks of cannabis smoking, little research has evaluated how ingestion differs from other methods of cannabis administration in terms of therapeutic efficacy, subjective effects, and safety. The most prominent difference between ingestion and inhalation of cannabis extracts is the delayed onset of drug effect with ingestion. Consumers often do not understand this aspect of edible use and may consume a greater than intended amount of drug before the drug has taken effect, often resulting in profoundly adverse effects. Written for the educated layperson and for policy makers, this paper explores the current state of research regarding edibles, highlighting the promises and challenges that edibles present to both users and policy makers, and describes the approaches that four states in which recreational cannabis use is legal have taken regarding regulating edibles.

Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways.

PubMed

Verhoeckx, Kitty C M; Korthout, Henrie A A J; van Meeteren-Kreikamp, A P; Ehlert, Karl A; Wang, Mei; van der Greef, Jan; Rodenburg, Richard J T; Witkamp, Renger F

2006-04-01

There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Delta(9)-tetrahydrocannabinol (THC), e.g. psychoactive properties. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa extracts and its main non-psychoactive constituent Delta(9)-tetrahydrocanabinoid acid (THCa). By heating Cannabis extracts, THCa was shown to be converted into THC. Unheated Cannabis extract and THCa were able to inhibit the tumor necrosis factor alpha (TNF-alpha) levels in culture supernatants from U937 macrophages and peripheral blood macrophages after stimulation with LPS in a dose-dependent manner. This inhibition persisted over a longer period of time, whereas after prolonged exposure time THC and heated Cannabis extract tend to induce the TNF-alpha level. Furthermore we demonstrated that THCa and THC show distinct effects on phosphatidylcholine specific phospholipase C (PC-PLC) activity. Unheated Cannabis extract and THCa inhibit the PC-PLC activity in a dose-dependent manner, while THC induced PC-PLC activity at high concentrations. These results suggest that THCa and THC exert their immuno-modulating effects via different metabolic pathways.

Cannabidiol rather than Cannabis sativa extracts inhibit cell growth and induce apoptosis in cervical cancer cells.

PubMed

Lukhele, Sindiswa T; Motadi, Lesetja R

2016-09-01

Cervical cancer remains a global health related issue among females of Sub-Saharan Africa, with over half a million new cases reported each year. Different therapeutic regimens have been suggested in various regions of Africa, however, over a quarter of a million women die of cervical cancer, annually. This makes it the most lethal cancer amongst black women and calls for urgent therapeutic strategies. In this study we compare the anti-proliferative effects of crude extract of Cannabis sativa and its main compound cannabidiol on different cervical cancer cell lines. To achieve our aim, phytochemical screening, MTT assay, cell growth analysis, flow cytometry, morphology analysis, Western blot, caspase 3/7 assay, and ATP measurement assay were conducted. Results obtained indicate that both cannabidiol and Cannabis sativa extracts were able to halt cell proliferation in all cell lines at varying concentrations. They further revealed that apoptosis was induced by cannabidiol as shown by increased subG0/G1 and apoptosis through annexin V. Apoptosis was confirmed by overexpression of p53, caspase 3 and bax. Apoptosis induction was further confirmed by morphological changes, an increase in Caspase 3/7 and a decrease in the ATP levels. In conclusion, these data suggest that cannabidiol rather than Cannabis sativa crude extracts prevent cell growth and induce cell death in cervical cancer cell lines.

Tasty THC: Promises and Challenges of Cannabis Edibles

PubMed Central

Barrus, Daniel G.; Capogrossi, Kristen L.; Cates, Sheryl C.; Gourdet, Camille K.; Peiper, Nicholas C.; Novak, Scott P.; Lefever, Timothy W.; Wiley, Jenny L.

2016-01-01

Food products containing cannabis extract (edibles) have emerged as a popular and lucrative facet of the legalized market for both recreational and medicinal cannabis. The many formulations of cannabis extracts used in edibles present a unique regulatory challenge for policy makers. Though edibles are often considered a safe, discreet, and effective means of attaining the therapeutic and/or intoxicating effects of cannabis without exposure to the potentially harmful risks of cannabis smoking, little research has evaluated how ingestion differs from other methods of cannabis administration in terms of therapeutic efficacy, subjective effects, and safety. The most prominent difference between ingestion and inhalation of cannabis extracts is the delayed onset of drug effect with ingestion. Consumers often do not understand this aspect of edible use and may consume a greater than intended amount of drug before the drug has taken effect, often resulting in profoundly adverse effects. Written for the educated layperson and for policy makers, this paper explores the current state of research regarding edibles, highlighting the promises and challenges that edibles present to both users and policy makers, and describes the approaches that four states in which recreational cannabis use is legal have taken regarding regulating edibles. PMID:28127591

Medicinal cannabis: is delta9-tetrahydrocannabinol necessary for all its effects?

PubMed

Wilkinson, J D; Whalley, B J; Baker, D; Pryce, G; Constanti, A; Gibbons, S; Williamson, E M

2003-12-01

Cannabis is under clinical investigation to assess its potential for medicinal use, but the question arises as to whether there is any advantage in using cannabis extracts compared with isolated Delta9-trans-tetrahydrocannabinol (Delta9THC), the major psychoactive component. We have compared the effect of a standardized cannabis extract (SCE) with pure Delta9THC, at matched concentrations of Delta9THC, and also with a Delta9THC-free extract (Delta9THC-free SCE), using two cannabinoid-sensitive models, a mouse model of multiple sclerosis (MS), and an in-vitro rat brain slice model of epilepsy. Whilst SCE inhibited spasticity in the mouse model of MS to a comparable level, it caused a more rapid onset of muscle relaxation, and a reduction in the time to maximum effect compared with Delta9THC alone. The Delta9THC-free extract or cannabidiol (CBD) caused no inhibition of spasticity. However, in the in-vitro epilepsy model, in which sustained epileptiform seizures were induced by the muscarinic receptor agonist oxotremorine-M in immature rat piriform cortical brain slices, SCE was a more potent and again more rapidly-acting anticonvulsant than isolated Delta9THC, but in this model, the Delta9THC-free extract also exhibited anticonvulsant activity. Cannabidiol did not inhibit seizures, nor did it modulate the activity of Delta9THC in this model. Therefore, as far as some actions of cannabis were concerned (e.g. antispasticity), Delta9THC was the active constituent, which might be modified by the presence of other components. However, for other effects (e.g. anticonvulsant properties) Delta9THC, although active, might not be necessary for the observed effect. Above all, these results demonstrated that not all of the therapeutic actions of cannabis herb might be due to the Delta9THC content.

Variation in cannabis potency and prices in a newly legal market: evidence from 30 million cannabis sales in Washington state.

PubMed

Smart, Rosanna; Caulkins, Jonathan P; Kilmer, Beau; Davenport, Steven; Midgette, Greg

2017-12-01

To (1) assess trends and variation in the market share of product types and potency sold in a legal cannabis retail market and (2) estimate how potency and purchase quantity influence price variation for cannabis flower. Secondary analysis of publicly available data from Washington State's cannabis traceability system spanning 7 July 2014 to 30 September 2016. Descriptive statistics and linear regressions assessed variation and trends in cannabis product variety and potency. Hedonic regressions estimated how purchase quantity and potency influence cannabis flower price variation. Washington State, USA. (1) A total of 44 482 176 million cannabis purchases, including (2) 31 052 123 cannabis flower purchases after trimming price and quantity outliers. Primary outcome measures were (1) monthly expenditures on cannabis, total delta-9-tetrahydrocannabinol (THC) concentration and cannabidiol (CBD) concentration by product type and (2) excise tax-inclusive price per gram of cannabis flower. Key covariates for the hedonic price regressions included quantity purchased, THC and CBD. Traditional cannabis flowers still account for the majority of spending (66.6%), but the market share of extracts for inhalation increased by 145.8% between October 2014 and September 2016, now comprising 21.2% of sales. The average THC-level for cannabis extracts is more than triple that for cannabis flowers (68.7% compared to 20.6%). For flower products, there is a statistically significant relationship between price per gram and both THC [coefficient = 0.012; 95% confidence interval (CI) = 0.011-0.013] and CBD (coefficient = 0.017; CI = 0.015-0.019). The estimated discount elasticity is -0.06 (CI = -0.07 to -0.05). In the state of Washington, USA, the legal cannabis market is currently dominated by high-THC cannabis flower, and features growing expenditures on extracts. For cannabis flower, both THC and CBD are associated with higher per-gram prices, and there are small but

The therapeutic potential of cannabis and cannabinoids.

PubMed

Grotenhermen, Franjo; Müller-Vahl, Kirsten

2012-07-01

Cannabis-based medications have been a topic of intense study since the endogenous cannabinoid system was discovered two decades ago. In 2011, for the first time, a cannabis extract was approved for clinical use in Germany. Selective literature review. Cannabis-based medications exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). More than 100 controlled clinical trials of cannabinoids or whole-plant preparations for various indications have been conducted since 1975. The findings of these trials have led to the approval of cannabis-based medicines (dronabinol, nabilone, and a cannabis extract [THC:CBD=1:1]) in several countries. In Germany, a cannabis extract was approved in 2011 for the treatment of moderate to severe refractory spasticity in multiple sclerosis. It is commonly used off label for the treatment of anorexia, nausea, and neuropathic pain. Patients can also apply for government permission to buy medicinal cannabis flowers for self-treatment under medical supervision. The most common side effects of cannabinoids are tiredness and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. There is now clear evidence that cannabinoids are useful for the treatment of various medical conditions.

Pro-resolution, protective and anti-nociceptive effects of a cannabis extract in the rat gastrointestinal tract.

PubMed

Wallace, J L; Flannigan, K L; McKnight, W; Wang, L; Ferraz, J G P; Tuitt, D

2013-04-01

Cannabis is widely used for treating a number of gastrointestinal ailments, but its use is associated with several adverse effects, particularly when the route of administration is via smoking. In the present study, we tested the effects (in rats) of a simple extract of medicinal cannabis (called "MFF") for its ability to promote resolution of colitis, to prevent gastric damage induced by naproxen, and to reduce gastric distention-induced visceral pain. Intracolonic, but not oral administration of MFF dose-dependently reduced the severity of hapten-induced colitis, an effect not reduced by pretreatment with antagonists of CB1 or CB2 receptors. Significant improvement of symptoms (diarrhea, weight loss) and healing of ulcerated tissue was evident with MFF treatment at doses that did not produce detectable urinary levels of 9-Δ-tetrahydrocannabinol (THC). MFF increased colonic hydrogen sulfide synthesis in healthy rats, but not in rats with colitis, and had no effect on colonic prostaglandin E2 synthesis. Orally, but not systemically administered MFF dose-dependently reduced the severity of naproxen-induced gastric damage, and a CB1 antagonist reversed this effect. MFF prevented gastric distention-induced visceral pain via a CB2-dependent mechanism. These results demonstrate that a simple extract of medicinal cannabis can significantly enhance resolution of inflammation and injury, as well as prevent injury, in the gastrointestinal tract. Interestingly, different cannabinoid receptors were involved in some of the effects. MFF may serve as the basis for a simple preparation of cannabis that would produce beneficial effects in the GI tract with reduced systemic toxicity.

Intravenous administration of cannabis and lethal anaphylaxis.

PubMed

Gilbert, John D; Grabowski, Marc; Byard, Roger W

2017-04-01

Cannabis allergy appears to be increasing. A 33-year-old woman is reported who collapsed and died shortly after injecting herself with a cannabis solution prepared by pouring boiling water onto plant material. There were no significant findings at autopsy, except for a single recent venepuncture wound in the left cubital fossa. Toxicological examination of the blood revealed low levels of methylamphetamine and amphetamine with tetrahydrocannabinol (Δ 9 -THC) and 11-nor-9-carboxy-Δ 9 -THC, and no opiates. The syringe used by the decedent contained Δ 9 -THC. Serum tryptase levels were markedly elevated (>200 µg/L; N < 12 µg/L). This finding coupled with the sudden collapse after injecting an aqueous extract of cannabis indicated a likely anaphylactic or anaphylactoid reaction to the extract. Cannabis allergy may occur following handling, inhalation, swallowing or injecting Cannabis sativa plants or their products. The possibility of an allergic reaction should therefore be considered at autopsy in deaths where there has been recent contact with cannabis.

Exposure to cannabis in popular music and cannabis use among adolescents.

PubMed

Primack, Brian A; Douglas, Erika L; Kraemer, Kevin L

2010-03-01

Cannabis use is referenced frequently in American popular music, yet it remains uncertain whether exposure to these references is associated with actual cannabis use. We aimed to determine if exposure to cannabis in popular music is associated independently with current cannabis use in a cohort of urban adolescents. We surveyed all 9th grade students at three large US urban high schools. We estimated participants' exposure to lyrics referent to cannabis with overall music exposure and content analyses of their favorite artists' songs. Outcomes included current (past 30 days) and ever use of cannabis. We used multivariable regression to assess independent associations between exposures and outcomes while controlling for important covariates. Each of the 959 participants was exposed to an estimated 27 cannabis references per day [correction added on 19 January 2010, after first online publication: 40 has been changed to 27] (standard deviation = 73 [correction added on 19 January 2010, after first online publication: 104 has been changed to 73]). Twelve per cent (n = 108) were current cannabis users and 32% (n = 286) had ever used cannabis. Compared with those in the lowest tertile of total cannabis exposure in music, those in the highest tertile of exposure were almost twice as likely to have used cannabis in the past 30 days (odds ratio = 1.83; 95% confidence interval = 1.04, 3.22), even after adjusting for socio-demographic variables, personality characteristics and parenting style. As expected, however, there was no significant relationship between our cannabis exposure variable and a sham outcome variable of alcohol use. This study supports an independent association between exposure to cannabis in popular music and early cannabis use among urban American adolescents.

Cannabis exacerbates depressive symptoms in rat model induced by reserpine.

PubMed

Khadrawy, Yasser A; Sawie, Hussein G; Abdel-Salam, Omar M E; Hosny, Eman N

2017-05-01

Cannabis sativa is one of the most widely recreational drugs and its use is more prevalent among depressed patients. Some studies reported that Cannabis has antidepressant effects while others showed increased depressive symptoms in Cannabis users. Therefore, the present study aims to investigate the effect of Cannabis extract on the depressive-like rats. Twenty four rats were divided into: control, rat model of depression induced by reserpine and depressive-like rats treated with Cannabis sativa extract (10mg/kg expressed as Δ9-tetrahydrocannabinol). The depressive-like rats showed a severe decrease in motor activity as assessed by open field test (OFT). This was accompanied by a decrease in monoamine levels and a significant increase in acetylcholinesterase activity in the cortex and hippocampus. Na + ,K + -ATPase activity increased in the cortex and decreased in the hippocampus of rat model. In addition, a state of oxidative stress was evident in the two brain regions. This was indicated from the significant increase in the levels of lipid peroxidation and nitric oxide. No signs of improvement were observed in the behavioral and neurochemical analyses in the depressive-like rats treated with Cannabis extract. Furthermore, Cannabis extract exacerbated the lipid peroxidation in the cortex and hippocampus. According to the present findings, it could be concluded that Cannabis sativa aggravates the motor deficits and neurochemical changes induced in the cortex and hippocampus of rat model of depression. Therefore, the obtained results could explain the reported increase in the depressive symptoms and memory impairment among Cannabis users. Copyright © 2017 Elsevier B.V. All rights reserved.

Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting.

PubMed

Duran, Marta; Pérez, Eulàlia; Abanades, Sergio; Vidal, Xavier; Saura, Cristina; Majem, Margarita; Arriola, Edurne; Rabanal, Manel; Pastor, Antoni; Farré, Magí; Rams, Neus; Laporte, Joan-Ramon; Capellà, Dolors

2010-11-01

Despite progress in anti-emetic treatment, many patients still suffer from chemotherapy-induced nausea and vomiting (CINV). This is a pilot, randomized, double-blind, placebo-controlled phase II clinical trial designed to evaluate the tolerability, preliminary efficacy, and pharmacokinetics of an acute dose titration of a whole-plant cannabis-based medicine (CBM) containing delta-9-tetrahydrocannabinol and cannabidiol, taken in conjunction with standard therapies in the control of CINV. Patients suffering from CINV despite prophylaxis with standard anti-emetic treatment were randomized to CBM or placebo, during the 120 h post-chemotherapy period, added to standard anti-emetic treatment. Tolerability was measured as the number of withdrawals from the study during the titration period because of adverse events (AEs). The endpoint for the preliminary efficacy analysis was the proportion of patients showing complete or partial response. Seven patients were randomized to CBM and nine to placebo. Only one patient in the CBM arm was withdrawn due to AEs. A higher proportion of patients in the CBM group experienced a complete response during the overall observation period [5/7 (71.4%) with CMB vs. 2/9 (22.2%) with placebo, the difference being 49.2% (95% CI 1%, 75%)], due to the delayed period. The incidence of AEs was higher in the CBM group (86% vs. 67%). No serious AEs were reported. The mean daily dose was 4.8 sprays in both groups. Compared with placebo, CBM added to standard antiemetic therapy was well tolerated and provided better protection against delayed CINV. These results should be confirmed in a phase III clinical trial. © 2010 Department of Health, Generalitat of Catalonia. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.

Quality of Web-Based Information on Cannabis Addiction

ERIC Educational Resources Information Center

Khazaal, Yasser; Chatton, Anne; Cochand, Sophie; Zullino, Daniele

2008-01-01

This study evaluated the quality of Web-based information on cannabis use and addiction and investigated particular content quality indicators. Three keywords ("cannabis addiction," "cannabis dependence," and "cannabis abuse") were entered into two popular World Wide Web search engines. Websites were assessed with a standardized proforma designed…

The effect of cannabis on tremor in patients with multiple sclerosis.

PubMed

Fox, P; Bain, P G; Glickman, S; Carroll, C; Zajicek, J

2004-04-13

Disabling tremor is common in patients with multiple sclerosis (MS). Data from animal model experiments and subjective and small objective studies involving patients suggest that cannabis may be an effective treatment for tremor associated with MS. To our knowledge, there are no published double-blind randomized controlled trials of cannabis as a treatment for tremor in MS patients. The authors conducted a randomized double-blind placebo-controlled crossover trial to examine the effect of oral cannador (cannabis extract) on 14 patients with MS with upper limb tremors. There were eight women and six men, with a mean age of 45 years and mean Expanded Disability Status Scale score of 6.25. Patients were randomly assigned to receive each treatment and the doses escalated over a 2-week period before each assessment. The primary outcome was change on a tremor index, measured using a validated tremor rating scale. The study was powered to detect a functionally significant 50% improvement in the tremor index. Secondary outcomes included accelerometry, an ataxia scale, spiral drawing, finger tapping, and nine-hole pegboard test performance. Analysis of the data showed no significant improvement in any of the objective measures of upper limb tremor with cannabis extract compared to placebo. Finger tapping was faster on placebo compared to cannabis extract (p < 0.02). However, there was a nonsignificant trend for patients to experience more subjective relief from their tremors while on cannabis extract compared to placebo. Cannabis extract does not produce a functionally significant improvement in MS-associated tremor.

Simultaneous and sensitive analysis of THC, 11-OH-THC, THC-COOH, CBD, and CBN by GC-MS in plasma after oral application of small doses of THC and cannabis extract.

PubMed

Nadulski, Thomas; Sporkert, Frank; Schnelle, Martin; Stadelmann, Andreas M; Roser, Patrik; Schefter, Tom; Pragst, Fritz

2005-01-01

Besides the psychoactive Delta(9)-tetrahydrocannabinol (THC), hashish and marijuana as well as cannabis-based medicine extracts contain varying amounts of cannabidiol (CBD) and of the degradation product cannabinol (CBN). The additional determination of these compounds is interesting from forensic and medical points of view because it can be used for further proof of cannabis exposure and because CBD is known to modify the effects of THC. Therefore, a method for the simultaneous quantitative determination of THC, its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH), CBD and CBN from plasma was developed. The method was based on automatic solid-phase extraction with C(18) ec columns, derivatization with N,O-bistrimethylsilyltrifluoroacetamide (BSTFA), and gas chromatography-electron impact ionization-mass spectrometry (GC-EI-MS) with deuterated standards. The limits of detection were between 0.15 and 0.29 ng/mL for THC, 11-OH-THC, THC-COOH, and CBD and 1.1 ng/mL for CBN. The method was applied in a prospective pharmacokinetic study after single oral administration of 10 mg THC alone or together with 5.4 mg CBD in cannabis extract. The maximum plasma concentrations after cannabis extract administration ranged between 1.2 and 10.3 ng/mL (mean 4.05 ng/mL) for THC, 1.8 and 12.3 ng/mL (mean 4.9 ng/mL) for 11-OH-THC, 19 and 71 ng/mL (mean 35 ng/mL) for THC-COOH, and 0.2 and 2.6 ng/mL (mean 0.95 ng/mg) for CBD. The peak concentrations (mean values) of THC, 11-OH-THC, THC-COOH, and CBD were observed at 56, 82, 115, and 60 min, respectively, after intake. CBN was not detected. Caused by the strong first-pass metabolism, the concentrations of the metabolites were increased during the first hours after drug administration when compared to literature data for smoking. Therefore, the concentration ratio 11-OH-THC/THC was discussed as a criterion for distinguishing oral from inhalative cannabis

Multiple sclerosis and extract of cannabis: results of the MUSEC trial.

PubMed

Zajicek, John Peter; Hobart, Jeremy C; Slade, Anita; Barnes, David; Mattison, Paul G

2012-11-01

Multiple sclerosis (MS) is associated with chronic symptoms, including muscle stiffness, spasms, pain and insomnia. Here we report the results of the Multiple Sclerosis and Extract of Cannabis (MUSEC) study that aimed to substantiate the patient based findings of previous studies. Patients with stable MS at 22 UK centres were randomised to oral cannabis extract (CE) (N=144) or placebo (N=135), stratified by centre, walking ability and use of antispastic medication. This double blind, placebo controlled, phase III study had a screening period, a 2 week dose titration phase from 5 mg to a maximum of 25 mg of tetrahydrocannabinol daily and a 10 week maintenance phase. The primary outcome measure was a category rating scale (CRS) measuring patient reported change in muscle stiffness from baseline. Further CRSs assessed body pain, spasms and sleep quality. Three validated MS specific patient reported outcome measures assessed aspects of spasticity, physical and psychological impact, and walking ability. The rate of relief from muscle stiffness after 12 weeks was almost twice as high with CE than with placebo (29.4% vs. 15.7%; OR 2.26; 95% CI 1.24 to 4.13; p=0.004, one sided). Similar results were found after 4 weeks and 8 weeks, and also for all further CRSs. Results from the MS scales supported these findings. The study met its primary objective to demonstrate the superiority of CE over placebo in the treatment of muscle stiffness in MS. This was supported by results for secondary efficacy variables. Adverse events in participants treated with CE were consistent with the known side effects of cannabinoids. No new safety concerns were observed. NCT00552604.

Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract.

PubMed

Nadulski, Thomas; Pragst, Fritz; Weinberg, Gordon; Roser, Patrik; Schnelle, Martin; Fronk, Eva-Maria; Stadelmann, Andreas Michael

2005-12-01

Cannabidiol (CBD) is known to modify the effects of Delta-tetrahydrocannabinol (THC) by decreasing anxiety and antagonizing other THC-effects. As a reason, pharmacodynamic as well as pharmacokinetic mechanisms were suggested. In context of the use of cannabis-based medicine extracts for therapeutic purposes, a study was performed in a double-blind and placebo-controlled cross-over design in which each of 24 volunteers (12 male and 12 female, age 18-45 years) obtained soft-gelatin capsules with 10 mg THC (THC-set), cannabis extract containing 10 mg THC +5.4 mg CBD (CAN-set) or placebo in weekly intervals. Blood samples were taken 30 minutes before and 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours and 24 hours after the intake. The concentrations of THC, of its metabolites 11-OH-THC, THC-COOH and of CBD in the plasma samples were determined by automatic solid phase extraction, derivatization with N,O-bis(trimethylsilyl)triflouroacetamide and gas chromatography-mass spectrometry. The concentration versus time curves (maximum concentrations Cmax, corresponding time tmax and areas under the curves AUC) were evaluated by statistical methods with respect to equivalence or differences between the CAN-set and the THC-set. Furthermore, the intra-individual ratios of Cmax and AUC for 11-OH-THC/THC, THC-COOH/THC and THC-COOH/11-OH-THC were compared between the THC-set and the CAN-set. Despite the large variation of the data, evidence emerged from the total of the results that CBD partially inhibits the CYP 2C catalyzed hydroxylation of THC to 11-OH-THC. The probability for this inhibition is particularly high for oral intake because THC and CBD attain relatively high concentrations in the liver and because of the high first-pass metabolism of THC. However, the effect of CBD is small in comparison to the variability caused by other factors. Therefore, a pharmacokinetic reason for the differences determined between pure THC and cannabis extract is improbable at

¹H NMR and HPLC/DAD for Cannabis sativa L. chemotype distinction, extract profiling and specification.

PubMed

Peschel, Wieland; Politi, Matteo

2015-08-01

The medicinal use of different chemovars and extracts of Cannabis sativa L. requires standardization beyond ∆9-tetrahydrocannabinol (THC) with complementing methods. We investigated the suitability of (1)H NMR key signals for distinction of four chemotypes measured in deuterated dimethylsulfoxide together with two new validated HPLC/DAD methods used for identification and extract profiling based on the main pattern of cannabinoids and other phenolics alongside the assayed content of THC, cannabidiol (CBD), cannabigerol (CBG) their acidic counterparts (THCA, CBDA, CBGA), cannabinol (CBN) and cannflavin A and B. Effects on cell viability (MTT assay, HeLa) were tested. The dominant cannabinoid pairs allowed chemotype recognition via assignment of selective proton signals and via HPLC even in cannabinoid-low extracts from the THC, CBD and CBG type. Substantial concentrations of cannabinoid acids in non-heated extracts suggest their consideration for total values in chemotype distinction and specifications of herbal drugs and extracts. Cannflavin A/B are extracted and detected together with cannabinoids but always subordinated, while other phenolics can be accumulated via fractionation and detected in a wide fingerprint but may equally serve as qualitative marker only. Cell viability reduction in HeLa was more determined by the total cannabinoid content than by the specific cannabinoid profile. Therefore the analysis and labeling of total cannabinoids together with the content of THC and 2-4 lead cannabinoids are considered essential. The suitability of analytical methods and the range of compound groups summarized in group and ratio markers are discussed regarding plant classification and pharmaceutical specification. Copyright © 2015 Elsevier B.V. All rights reserved.

Quantitative Determination of Cannabinoids in Cannabis and Cannabis Products Using Ultra-High-Performance Supercritical Fluid Chromatography and Diode Array/Mass Spectrometric Detection.

PubMed

Wang, Mei; Wang, Yan-Hong; Avula, Bharathi; Radwan, Mohamed M; Wanas, Amira S; Mehmedic, Zlatko; van Antwerp, John; ElSohly, Mahmoud A; Khan, Ikhlas A

2017-05-01

Ultra-high-performance supercritical fluid chromatography (UHPSFC) is an efficient analytical technique and has not been fully employed for the analysis of cannabis. Here, a novel method was developed for the analysis of 30 cannabis plant extracts and preparations using UHPSFC/PDA-MS. Nine of the most abundant cannabinoids, viz. CBD, ∆ 8 -THC, THCV, ∆ 9 -THC, CBN, CBG, THCA-A, CBDA, and CBGA, were quantitatively determined (RSDs < 6.9%). Unlike GC methods, no derivatization or decarboxylation was required prior to UHPSFC analysis. The UHPSFC chromatographic separation of cannabinoids displayed an inverse elution order compared to UHPLC. Combining with PDA-MS, this orthogonality is valuable for discrimination of cannabinoids in complex matrices. The developed method was validated, and the quantification results were compared with a standard UHPLC method. The RSDs of these two methods were within ±13.0%. Finally, chemometric analysis including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to differentiate between cannabis samples. © 2016 American Academy of Forensic Sciences.

Cannabis and schizophrenia.

PubMed

McLoughlin, Benjamin C; Pushpa-Rajah, Jonathan A; Gillies, Donna; Rathbone, John; Variend, Hannele; Kalakouti, Eliana; Kyprianou, Katerina

2014-10-14

Schizophrenia is a mental illness causing disordered beliefs, ideas and sensations. Many people with schizophrenia smoke cannabis, and it is unclear why a large proportion do so and if the effects are harmful or beneficial. It is also unclear what the best method is to allow people with schizophrenia to alter their cannabis intake. To assess the effects of specific psychological treatments for cannabis reduction in people with schizophrenia.To assess the effects of antipsychotics for cannabis reduction in people with schizophrenia.To assess the effects of cannabinoids (cannabis related chemical compounds derived from cannabis or manufactured) for symptom reduction in people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register, 12 August 2013, which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE, PUBMED and PsycINFO.We searched all references of articles selected for inclusion for further relevant trials. We contacted the first author of included studies for unpublished trials or data. We included all randomised controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed:1) treatments to reduce cannabis use in people with schizophrenia;2) the effects of cannabinoids on people with schizophrenia. We independently inspected citations, selected papers and then re-inspected the studies if there were discrepancies, and extracted data. For dichotomous data we calculated risk ratios (RR) and for continuous data, we calculated mean differences (MD), both with 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. We excluded data if loss to follow-up was greater than 50%. We assessed risk of bias for included studies and used GRADE to rate the quality of the evidence. We identified eight randomised trials, involving 530 participants, which met our selection criteria.For the cannabis reduction studies no one treatment showed superiority for reduction

Antihyperalgesic effect of a Cannabis sativa extract in a rat model of neuropathic pain: mechanisms involved.

PubMed

Comelli, Francesca; Giagnoni, Gabriella; Bettoni, Isabella; Colleoni, Mariapia; Costa, Barbara

2008-08-01

This study aimed to give a rationale for the employment of phytocannabinoid formulations to treat neuropathic pain. It was found that a controlled cannabis extract, containing multiple cannabinoids, in a defined ratio, and other non-cannabinoid fractions (terpenes and flavonoids) provided better antinociceptive efficacy than the single cannabinoid given alone, when tested in a rat model of neuropathic pain. The results also demonstrated that such an antihyperalgesic effect did not involve the cannabinoid CB1 and CB2 receptors, whereas it was mediated by vanilloid receptors TRPV1. The non-psychoactive compound, cannabidiol, is the only component present at a high level in the extract able to bind to this receptor: thus cannabidiol was the drug responsible for the antinociceptive behaviour observed. In addition, the results showed that after chronic oral treatment with cannabis extract the hepatic total content of cytochrome P450 was strongly inhibited as well as the intestinal P-glycoprotein activity. It is suggested that the inhibition of hepatic metabolism determined an increased bioavailability of cannabidiol resulting in a greater effect. However, in the light of the well known antioxidant and antiinflammatory properties of terpenes and flavonoids which could significantly contribute to the therapeutic effects, it cannot be excluded that the synergism observed might be achieved also in the absence of the cytochrome P450 inhibition.

Cannabis-induced impairment of learning and memory: effect of different nootropic drugs.

PubMed

Abdel-Salam, Omar M E; Salem, Neveen A; El-Sayed El-Shamarka, Marwa; Al-Said Ahmed, Noha; Seid Hussein, Jihan; El-Khyat, Zakaria A

2013-01-01

Cannabis sativa preparations are the most commonly used illicit drugs worldwide. The present study aimed to investigate the effect of Cannabis sativa extract in the working memory version of the Morris water maze (MWM; Morris, 1984[43]) test and determine the effect of standard memory enhancing drugs. Cannabis sativa was given at doses of 5, 10 or 20 mg/kg (expressed as Δ(9)-tetrahydrocannabinol) alone or co-administered with donepezil (1 mg/kg), piracetam (150 mg/ kg), vinpocetine (1.5 mg/kg) or ginkgo biloba (25 mg/kg) once daily subcutaneously (s.c.) for one month. Mice were examined three times weekly for their ability to locate a submerged platform. Mice were euthanized 30 days after starting cannabis injection when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, glucose and brain monoamines were determined. Cannabis resulted in a significant increase in the time taken to locate the platform and enhanced the memory impairment produced by scopolamine. This effect of cannabis decreased by memory enhancing drugs with piracetam resulting in the most-shorter latency compared with the cannabis. Biochemically, cannabis altered the oxidative status of the brain with decreased MDA, increased GSH, but decreased nitric oxide and glucose. In cannabis-treated rats, the level of GSH in brain was increased after vinpocetine and donepezil and was markedly elevated after Ginkgo biloba. Piracetam restored the decrease in glucose and nitric oxide by cannabis. Cannabis caused dose-dependent increases of brain serotonin, noradrenaline and dopamine. After cannabis treatment, noradrenaline is restored to its normal value by donepezil, vinpocetine or Ginkgo biloba, but increased by piracetam. The level of dopamine was significantly reduced by piracetam, vinpocetine or Ginkgo biloba. These data indicate that cannabis administration is associated with impaired memory performance which is likely to involve decreased brain glucose

Cannabis-induced impairment of learning and memory: effect of different nootropic drugs

PubMed Central

Abdel-Salam, Omar M.E.; Salem, Neveen A.; El-Sayed El-Shamarka, Marwa; Al-Said Ahmed, Noha; Seid Hussein, Jihan; El-Khyat, Zakaria A.

2013-01-01

Cannabis sativa preparations are the most commonly used illicit drugs worldwide. The present study aimed to investigate the effect of Cannabis sativa extract in the working memory version of the Morris water maze (MWM; Morris, 1984[43]) test and determine the effect of standard memory enhancing drugs. Cannabis sativa was given at doses of 5, 10 or 20 mg/kg (expressed as Δ9-tetrahydrocannabinol) alone or co-administered with donepezil (1 mg/kg), piracetam (150 mg/ kg), vinpocetine (1.5 mg/kg) or ginkgo biloba (25 mg/kg) once daily subcutaneously (s.c.) for one month. Mice were examined three times weekly for their ability to locate a submerged platform. Mice were euthanized 30 days after starting cannabis injection when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, glucose and brain monoamines were determined. Cannabis resulted in a significant increase in the time taken to locate the platform and enhanced the memory impairment produced by scopolamine. This effect of cannabis decreased by memory enhancing drugs with piracetam resulting in the most-shorter latency compared with the cannabis. Biochemically, cannabis altered the oxidative status of the brain with decreased MDA, increased GSH, but decreased nitric oxide and glucose. In cannabis-treated rats, the level of GSH in brain was increased after vinpocetine and donepezil and was markedly elevated after Ginkgo biloba. Piracetam restored the decrease in glucose and nitric oxide by cannabis. Cannabis caused dose-dependent increases of brain serotonin, noradrenaline and dopamine. After cannabis treatment, noradrenaline is restored to its normal value by donepezil, vinpocetine or Ginkgo biloba, but increased by piracetam. The level of dopamine was significantly reduced by piracetam, vinpocetine or Ginkgo biloba. These data indicate that cannabis administration is associated with impaired memory performance which is likely to involve decreased brain glucose

The use of pesticides in Belgian illicit indoor cannabis plantations.

PubMed

Cuypers, Eva; Vanhove, Wouter; Gotink, Joachim; Bonneure, Arne; Van Damme, Patrick; Tytgat, Jan

2017-08-01

Cannabis (Cannabis spp.) use and cultivation continue to increase in many (European) countries. The illicit indoor cannabis plantations that supply Belgian and European cannabis markets create problems and concerns about health and safety of intervention staff, dismantling companies, the direct environment of cannabis plantations and, eventually, of cannabis users. Main risks may come from pesticide residues on plants, cultivation infrastructure and materials; left-over plant growth-promoting substances; mycotoxins from fungal pathogens on harvested plants; and/or high levels of cannabinoids in cannabis plant parts for consumption. In the present research, we report on pesticides found in illicit indoor cannabis plantations in Belgium. EN15662 QuEChERS extraction method and LC-MS/MS analysis were used to identify pesticides in indoor cannabis plantations and thus to evaluate the hazards associated with the use, cultivation and removal of cannabis plants in plantations as well as with dismantling activities in the cultivation rooms. We found pesticides in 64.3% of 72 cannabis plant samples and in 65.2% of 46 carbon filter cloth samples. Overall, 19 pesticides belonging to different chemical classes were identified. We found o-phenylphenol, bifenazate, cypermethrin, imidacloprid, propamocarb, propiconazole and tebuconazole, which is consistent with the commonly reported pesticides from literature. In only a few cases, pesticides found in bottles with a commercial label, were also identified in plant or stagnant water samples collected from the growth rooms where the bottles had been collected. We further revealed that, even though most pesticides have a low volatility, they could be detected from the carbon filters hanging at the ceiling of cultivation rooms. As a result, it is likely that pesticides also prevail in the plantation atmosphere during and after cultivation. The risk of inhaling the latter pesticides increases when plants sprayed with pesticides are

[Results of a standardized survey on the medical use of cannabis products in the German-speaking area].

PubMed

Schnelle, M; Grotenhermen, F; Reif, M; Gorter, R W

1999-10-01

The plant Cannabis sativa has a long history of medical use in the treatment of pain and spasms, the promotion of sleep, and the suppression of nausea and vomiting. However, in the early 70s cannabis was classified in the Narcotic Acts in countries all over the world as having no therapeutic benefit; therefore, it cannot be prescribed by physicians or dispensed by pharmacists. In the light of this contradictory situation an increasing number of patients practices a self-prescription with cannabis products for relieving a variety of symptoms. An anonymous standardized survey of the medical use of cannabis and cannabis products of patients in Germany, Austria and Switzerland was conducted by the Association for Cannabis as Medicine (Cologne, Germany). During about one year 170 subjects participated in this survey; questionnaires of 128 patients could be included into the evaluation. 68% of these participants were males, 32% females, with a total mean age of 37.5 (+/- 9.6) years. The most frequently mentioned indications for medicinal cannabis use were depression (12.0%), multiple sclerosis (10.8%), HIV-infection (9.0%), migraine (6.6%), asthma (6.0%), back pain (5.4%), hepatitis C (4. 8%), sleeping disorders (4.8%), epilepsy (3.6%), spasticity (3.6%), headache (3.6%), alcoholism (3.0%), glaucoma (3.0%), nausea (3.0%), disk prolapse (2.4%), and spinal cord injury (2.4%). The majority of patients used natural cannabis products such as marihuana, hashish and an alcoholic tincture; in just 5 cases dronabinol (Marinol) was taken by prescription. About half of the 128 participants of the survey (52.4%) had used cannabis as a recreational drug before the onset of their illness. To date 14.3% took cannabis orally, 49.2% by inhalation and in 36.5% of cases both application modes were used. 72.2% of the patients stated the symptoms of their illness to have 'much improved' after cannabis ingestion, 23.4% stated to have 'slightly improved', 4.8% experienced 'no change' and 1

Pain, Cannabis Species, and Cannabis Use Disorders

PubMed Central

Cohen, Nicole L.; Heinz, Adrienne J.; Ilgen, Mark; Bonn-Miller, Marcel O.

2016-01-01

Objective: The purpose of this study was to examine whether individuals who used medical cannabis for chronic pain were at increased risk for cannabis use problems compared with individuals who used medical cannabis for other reasons (e.g., anxiety, insomnia, and muscle spasms). An additional aim was to determine whether individuals who used cannabis for chronic pain, as well as those who reported greater within-group pain levels, demonstrated a species preference (i.e., sativa, indica, hybrids) and the extent to which species preference was associated with cannabis use problems. Method: Participants were 163 medical cannabis users (77% male), recruited from a medical marijuana dispensary in California, who completed assessments of medical cannabis use motives, history, preferences (species type), and problems, as well as current pain level. Results: Individuals who used cannabis to manage chronic pain experienced fewer cannabis use problems than those who did not use it for pain; among those who used it for pain, the average pain level in the past week was not associated with cannabis use problems. Furthermore, individuals who used cannabis for chronic pain were more likely to use indica over sativa. Preference for indica was associated with fewer cannabis use problems than preference for hybrid species. Conclusions: Individuals who use cannabis to manage chronic pain may be at a lower risk for cannabis use problems, relative to individuals who use it for other indications, potentially as a function of their species preference. PMID:27172585

Pain, Cannabis Species, and Cannabis Use Disorders.

PubMed

Cohen, Nicole L; Heinz, Adrienne J; Ilgen, Mark; Bonn-Miller, Marcel O

2016-05-01

The purpose of this study was to examine whether individuals who used medical cannabis for chronic pain were at increased risk for cannabis use problems compared with individuals who used medical cannabis for other reasons (e.g., anxiety, insomnia, and muscle spasms). An additional aim was to determine whether individuals who used cannabis for chronic pain, as well as those who reported greater within-group pain levels, demonstrated a species preference (i.e., sativa, indica, hybrids) and the extent to which species preference was associated with cannabis use problems. Participants were 163 medical cannabis users (77% male), recruited from a medical marijuana dispensary in California, who completed assessments of medical cannabis use motives, history, preferences (species type), and problems, as well as current pain level. Individuals who used cannabis to manage chronic pain experienced fewer cannabis use problems than those who did not use it for pain; among those who used it for pain, the average pain level in the past week was not associated with cannabis use problems. Furthermore, individuals who used cannabis for chronic pain were more likely to use indica over sativa. Preference for indica was associated with fewer cannabis use problems than preference for hybrid species. Individuals who use cannabis to manage chronic pain may be at a lower risk for cannabis use problems, relative to individuals who use it for other indications, potentially as a function of their species preference.

Alteration of glucose metabolism in liver by acute administration of cannabis.

PubMed

Sanz, P; Rodríguez-Vicente, C; Repetto, M

1985-01-01

In previous research on the effects of cannabis on cellular functions the authors observed an increase in glucose metabolism in the postmitochondrial fraction of the liver of rats submitted to chronic administration of cannabis extracts. Continuing this research on rats submitted to acute cannabis intoxication a single dose of cannabis extract (600 mg/kg) in olive oil is administered to male adult rats and the animals are killed within a 36-hour period. The analyses show that energetic and detoxifying metabolism of glucose is increased, as indicated by the increase of F-1, 6-di P-aldolase and uridin-diphosphoglucose-dehydrogenase activities, which parallels the observed decrease of glycogen levels. Maximum effect appears between 8 and 16 hours after administration.

Anti-Inflammatory Activity in Colon Models Is Derived from Δ9-Tetrahydrocannabinolic Acid That Interacts with Additional Compounds in Cannabis Extracts

PubMed Central

Nallathambi, Rameshprabu; Mazuz, Moran; Ion, Aurel; Selvaraj, Gopinath; Weininger, Smadar; Fridlender, Marcelo; Nasser, Ahmad; Sagee, Oded; Kumari, Puja; Nemichenizer, Diana; Mendelovitz, Maayan; Firstein, Nave; Hanin, Orly; Konikoff, Fred; Kapulnik, Yoram; Naftali, Timna; Koltai, Hinanit

2017-01-01

Abstract Introduction: Inflammatory bowel diseases (IBDs) include Crohn's disease, and ulcerative colitis. Cannabis sativa preparations have beneficial effects for IBD patients. However, C. sativa extracts contain hundreds of compounds. Although there is much knowledge of the activity of different cannabinoids and their receptor agonists or antagonists, the cytotoxic and anti-inflammatory activity of whole C. sativa extracts has never been characterized in detail with in vitro and ex vivo colon models. Material and Methods: The anti-inflammatory activity of C. sativa extracts was studied on three lines of epithelial cells and on colon tissue. C. sativa flowers were extracted with ethanol, enzyme-linked immunosorbent assay was used to determine the level of interleukin-8 in colon cells and tissue biopsies, chemical analysis was performed using high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance and gene expression was determined by quantitative real-time PCR. Results: The anti-inflammatory activity of Cannabis extracts derives from D9-tetrahydrocannabinolic acid (THCA) present in fraction 7 (F7) of the extract. However, all fractions of C. sativa at a certain combination of concentrations have a significant increased cytotoxic activity. GPR55 receptor antagonist significantly reduces the anti-inflammatory activity of F7, whereas cannabinoid type 2 receptor antagonist significantly increases HCT116 cell proliferation. Also, cannabidiol (CBD) shows dose dependent cytotoxic activity, whereas anti-inflammatory activity was found only for the low concentration of CBD, and in a bell-shaped rather than dose-dependent manner. Activity of the extract and active fraction was verified on colon tissues taken from IBD patients, and was shown to suppress cyclooxygenase-2 (COX2) and metalloproteinase-9 (MMP9) gene expression in both cell culture and colon tissue. Conclusions: It is suggested that the anti-inflammatory activity of Cannabis

Anti-Inflammatory Activity in Colon Models Is Derived from Δ9-Tetrahydrocannabinolic Acid That Interacts with Additional Compounds in Cannabis Extracts.

PubMed

Nallathambi, Rameshprabu; Mazuz, Moran; Ion, Aurel; Selvaraj, Gopinath; Weininger, Smadar; Fridlender, Marcelo; Nasser, Ahmad; Sagee, Oded; Kumari, Puja; Nemichenizer, Diana; Mendelovitz, Maayan; Firstein, Nave; Hanin, Orly; Konikoff, Fred; Kapulnik, Yoram; Naftali, Timna; Koltai, Hinanit

2017-01-01

Introduction: Inflammatory bowel diseases (IBDs) include Crohn's disease, and ulcerative colitis. Cannabis sativa preparations have beneficial effects for IBD patients. However, C. sativa extracts contain hundreds of compounds. Although there is much knowledge of the activity of different cannabinoids and their receptor agonists or antagonists, the cytotoxic and anti-inflammatory activity of whole C. sativa extracts has never been characterized in detail with in vitro and ex vivo colon models. Material and Methods: The anti-inflammatory activity of C. sativa extracts was studied on three lines of epithelial cells and on colon tissue. C. sativa flowers were extracted with ethanol, enzyme-linked immunosorbent assay was used to determine the level of interleukin-8 in colon cells and tissue biopsies, chemical analysis was performed using high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance and gene expression was determined by quantitative real-time PCR. Results: The anti-inflammatory activity of Cannabis extracts derives from D9-tetrahydrocannabinolic acid (THCA) present in fraction 7 (F7) of the extract. However, all fractions of C. sativa at a certain combination of concentrations have a significant increased cytotoxic activity. GPR55 receptor antagonist significantly reduces the anti-inflammatory activity of F7, whereas cannabinoid type 2 receptor antagonist significantly increases HCT116 cell proliferation. Also, cannabidiol (CBD) shows dose dependent cytotoxic activity, whereas anti-inflammatory activity was found only for the low concentration of CBD, and in a bell-shaped rather than dose-dependent manner. Activity of the extract and active fraction was verified on colon tissues taken from IBD patients, and was shown to suppress cyclooxygenase-2 ( COX2 ) and metalloproteinase-9 ( MMP9 ) gene expression in both cell culture and colon tissue. Conclusions: It is suggested that the anti-inflammatory activity of Cannabis extracts

Cannabis for Chronic Pain: Challenges and Considerations.

PubMed

Romero-Sandoval, E Alfonso; Fincham, Jack E; Kolano, Ashley L; Sharpe, Brandi N; Alvarado-Vázquez, P Abigail

2018-06-01

The National Academies of Sciences, Engineering, and Medicine has found substantial evidence that cannabis (plant) is effective for the treatment of chronic pain in adults, and moderate evidence that oromucosal cannabinoids (extracts, especially nabiximols) improve short-term sleep disturbances in chronic pain. The paradoxical superiority of the cannabis plant over cannabinoid molecules represents a challenge for the medical community and the established processes that define modern pharmacy. The expanding and variable legalization of cannabis in multiple states nationwide represents an additional challenge for patients and the medical community because recreational and medicinal cannabis are irresponsibly overlapped. Cannabis designed for recreational use (containing high levels of active ingredients) is increasingly available to patients with chronic pain who do not find relief with current pharmacologic entities, which exposes patients to potential harm. This article analyzes the available scientific evidence to address controversial questions that the current state of cannabis poses for health care professionals and chronic pain patients and sets the basis for a more open discussion about the role of cannabis in modern medicine for pain management. A critical discussion on these points, the legal status of cannabis, and considerations for health care providers is presented. © 2018 Pharmacotherapy Publications, Inc.

An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse.

PubMed

Pagano, Ester; Capasso, Raffaele; Piscitelli, Fabiana; Romano, Barbara; Parisi, Olga A; Finizio, Stefania; Lauritano, Anna; Marzo, Vincenzo Di; Izzo, Angelo A; Borrelli, Francesca

2016-01-01

Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for "CBD botanical drug substance," on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage - after the inflammatory insult (curative protocol). The amounts of CBD in the colon, brain, and liver after the oral treatments were measured by high-performance liquid chromatography coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice) in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion) or orally (only at one dose). In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse

PubMed Central

Pagano, Ester; Capasso, Raffaele; Piscitelli, Fabiana; Romano, Barbara; Parisi, Olga A.; Finizio, Stefania; Lauritano, Anna; Marzo, Vincenzo Di; Izzo, Angelo A.; Borrelli, Francesca

2016-01-01

Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for “CBD botanical drug substance,” on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage – after the inflammatory insult (curative protocol). The amounts of CBD in the colon, brain, and liver after the oral treatments were measured by high-performance liquid chromatography coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice) in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion) or orally (only at one dose). In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment. PMID:27757083

Evaluating the Effects of Gamma-Irradiation for Decontamination of Medicinal Cannabis

PubMed Central

Hazekamp, Arno

2016-01-01

In several countries with a National medicinal cannabis program, pharmaceutical regulations specify that herbal cannabis products must adhere to strict safety standards regarding microbial contamination. Treatment by gamma irradiation currently seems the only method available to meet these requirements. We evaluated the effects of irradiation treatment of four different cannabis varieties covering different chemical compositions. Samples were compared before and after standard gamma-irradiation treatment by performing quantitative UPLC analysis of major cannabinoids, as well as qualitative GC analysis of full cannabinoid and terpene profiles. In addition, water content and microscopic appearance of the cannabis flowers was evaluated. This study found that treatment did not cause changes in the content of THC and CBD, generally considered as the most important therapeutically active components of medicinal cannabis. Likewise, the water content and the microscopic structure of the dried cannabis flowers were not altered by standard irradiation protocol in the cannabis varieties studied. The effect of gamma-irradiation was limited to a reduction of some terpenes present in the cannabis, but keeping the terpene profile qualitatively the same. Based on the results presented in this report, gamma irradiation of herbal cannabis remains the recommended method of decontamination, at least until other more generally accepted methods have been developed and validated. PMID:27199751

Evaluating the Effects of Gamma-Irradiation for Decontamination of Medicinal Cannabis.

PubMed

Hazekamp, Arno

2016-01-01

In several countries with a National medicinal cannabis program, pharmaceutical regulations specify that herbal cannabis products must adhere to strict safety standards regarding microbial contamination. Treatment by gamma irradiation currently seems the only method available to meet these requirements. We evaluated the effects of irradiation treatment of four different cannabis varieties covering different chemical compositions. Samples were compared before and after standard gamma-irradiation treatment by performing quantitative UPLC analysis of major cannabinoids, as well as qualitative GC analysis of full cannabinoid and terpene profiles. In addition, water content and microscopic appearance of the cannabis flowers was evaluated. This study found that treatment did not cause changes in the content of THC and CBD, generally considered as the most important therapeutically active components of medicinal cannabis. Likewise, the water content and the microscopic structure of the dried cannabis flowers were not altered by standard irradiation protocol in the cannabis varieties studied. The effect of gamma-irradiation was limited to a reduction of some terpenes present in the cannabis, but keeping the terpene profile qualitatively the same. Based on the results presented in this report, gamma irradiation of herbal cannabis remains the recommended method of decontamination, at least until other more generally accepted methods have been developed and validated.

Metabolic fingerprinting of Cannabis sativa L., cannabinoids and terpenoids for chemotaxonomic and drug standardization purposes.

PubMed

Fischedick, Justin Thomas; Hazekamp, Arno; Erkelens, Tjalling; Choi, Young Hae; Verpoorte, Rob

2010-12-01

Cannabis sativa L. is an important medicinal plant. In order to develop cannabis plant material as a medicinal product quality control and clear chemotaxonomic discrimination between varieties is a necessity. Therefore in this study 11 cannabis varieties were grown under the same environmental conditions. Chemical analysis of cannabis plant material used a gas chromatography flame ionization detection method that was validated for quantitative analysis of cannabis monoterpenoids, sesquiterpenoids, and cannabinoids. Quantitative data was analyzed using principal component analysis to determine which compounds are most important in discriminating cannabis varieties. In total 36 compounds were identified and quantified in the 11 varieties. Using principal component analysis each cannabis variety could be chemically discriminated. This methodology is useful for both chemotaxonomic discrimination of cannabis varieties and quality control of plant material. Copyright © 2010 Elsevier Ltd. All rights reserved.

Cannabis, 1977.

PubMed

1978-10-01

Recent advances in development of immunoassay methods for marijuana constituents in body fluids provide a rapid means of detection for forensic purposes and a useful research tool for accurate quantitation of dose-response relation. Therapeutic possibilities of cannabis, such as reduction in intraocular pressure and bronchodilatation, may stimulate development of synthetic cannabinoid derivatives that meet acceptable standards of safety and effiicacy for treatment of glaucoma and asthma. Cannabis use may have harmful short- and long-term impacts on health. Potentially serious short-term effects include predisposition to angina during exercise in patients with coronary artery disease. Even in healthy subjects, marijuana smoking decreases peak exercise performance, possibly because of its chronotropic effect with achievement of maximum heart rate at reduced work loads. Although no conclusive evidence exists for long-term biologic consequences of chronic cannabis use, preliminary evidence, suggesting impairment in pulmonary function and immune responses, requires further investigation with large-scale epidemiologic studies.

Determination of delta-9-tetrahydrocannabinol content of cannabis seizures in Egypt.

PubMed

Souleman, Ahmed M A; Gaafar, Alaa El-Din M; Abdel-Salam, Omar M; ElShebiney, Shaimaa A

2017-03-01

To determine the delta-9-tetrahydrocannabinol (THC) content of cannabis seizures in Egypt. Unheated and heated extracts of cannabis seizures were prepared from the dried flowering tops and leaves (marijuana) or from the resin (hashish) and subjected to analysis using high performance liquid chromatography (HPLC). The heated resin extract had the peak of THC in a relative ratio of 31.34%, while extracting the resin directly without heating contained only 18.34% of THC. On the other hand, marijuana showed minimum percentage of THC at 11.188% on heating and 9.55% without heating. These results indicate the high potency of the abused cannabis plant in the illicit Egyptian market. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Reaching out towards cannabis: approach-bias in heavy cannabis users predicts changes in cannabis use

PubMed Central

Cousijn, Janna; Goudriaan, Anna E; Wiers, Reinout W

2011-01-01

Aims Repeated drug exposure can lead to an approach-bias, i.e. the relatively automatically triggered tendencies to approach rather that avoid drug-related stimuli. Our main aim was to study this approach-bias in heavy cannabis users with the newly developed cannabis Approach Avoidance Task (cannabis-AAT) and to investigate the predictive relationship between an approach-bias for cannabis-related materials and levels of cannabis use, craving, and the course of cannabis use. Design, settings and participants Cross-sectional assessment and six-month follow-up in 32 heavy cannabis users and 39 non-using controls. Measurements Approach and avoidance action-tendencies towards cannabis and neutral images were assessed with the cannabis AAT. During the AAT, participants pulled or pushed a joystick in response to image orientation. To generate additional sense of approach or avoidance, pulling the joystick increased picture size while pushing decreased it. Craving was measured pre- and post-test with the multi-factorial Marijuana Craving Questionnaire (MCQ). Cannabis use frequencies and levels of dependence were measured at baseline and after a six-month follow-up. Findings Heavy cannabis users demonstrated an approach-bias for cannabis images, as compared to controls. The approach-bias predicted changes in cannabis use at six-month follow-up. The pre-test MCQ emotionality and expectancy factor were associated negatively with the approach-bias. No effects were found on levels of cannabis dependence. Conclusions Heavy cannabis users with a strong approach-bias for cannabis are more likely to increase their cannabis use. This approach-bias could be used as a predictor of the course of cannabis use to identify individuals at risk from increasing cannabis use. PMID:21518067

Cannabis Allergy: What do We Know Anno 2015.

PubMed

Decuyper, Ine; Ryckebosch, Hanne; Van Gasse, Athina L; Sabato, Vito; Faber, Margaretha; Bridts, Chris H; Ebo, Didier G

2015-10-01

For about a decade, IgE-mediated cannabis (marihuana) allergy seems to be on the rise. Both active and passive exposure to cannabis allergens may lead to a cannabis sensitization and/or allergy. The clinical manifestations of a cannabis allergy can vary from mild to life-threatening reactions, often depending on the route of exposure. In addition, sensitization to cannabis allergens can trigger various secondary cross-allergies, mostly for plant-derived food. This clinical entity, which we have designated as the "cannabis-fruit/vegetable syndrome" might also imply cross-reactivity with tobacco, latex and plant-food derived alcoholic beverages. These secondary cross-allergies are mainly described in Europe and appear to result from cross-reactivity between non-specific lipid transfer proteins or thaumatin-like proteins present in Cannabis sativa and their homologues that are ubiquitously distributed throughout plant kingdom. At present, diagnosis of cannabis-related allergies rests upon a thorough history completed with skin testing using native extracts from buds and leaves. However, quantification of specific IgE antibodies and basophil activation tests can also be helpful to establish correct diagnosis. In the absence of a cure, treatment comprises absolute avoidance measures including a stop of any further cannabis (ab)use.

Cannabis exposure associated with weight reduction and β-cell protection in an obese rat model.

PubMed

Levendal, R-A; Schumann, D; Donath, M; Frost, C L

2012-05-15

The aim of this study was to investigate the effect of an organic cannabis extract on β-cell secretory function in an in vivo diet-induced obese rat model and determine the associated molecular changes within pancreatic tissue. Diet-induced obese Wistar rats and rats fed on standard pellets were subcutaneously injected with an organic cannabis extract or the vehicle over a 28-day period. The effect of diet and treatment was evaluated using the intraperitoneal glucose tolerance tests (IPGTTs) and qPCR analysis on rat pancreata harvested upon termination of the experiment. The cafeteria diet induced an average weight difference of 32g and an overall increase in body weight in the experimental groups occurred at a significantly slower rate than the control groups, irrespective of diet. Area under the curve for glucose (AUC(g)) in the obese group was significantly lower compared to the lean group (p<0.001), with cannabis treatment significantly reducing the AUC(g) in the lean group (p<0.05), and remained unchanged in the obese group, relative to the obese control group. qPCR analysis showed that the cafeteria diet induced down-regulation of the following genes in the obese control group, relative to lean controls: UCP2, c-MYC and FLIP. Cannabis treatment in the obese group resulted in up-regulation of CB1, GLUT2, UCP2 and PKB, relative to the obese control group, while c-MYC levels were down-regulated, relative to the lean control group. Treatment did not significantly change gene expression in the lean group. These results suggest that the cannabis extract protects pancreatic islets against the negative effects of obesity. Copyright © 2012 Elsevier GmbH. All rights reserved.

Adverse effects of cannabis.

PubMed

2011-01-01

Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

A review of the world cannabis situation.

PubMed

Leggett, T

2006-01-01

Cannabis is the world's most widely cultivated and consumed illicit drug, but there remain major gaps in our understanding of global cannabis markets. For example, it appears that premium sinsemilla cannabis, often produced indoors in consumer countries, has become more potent in recent years and that its market share is also growing in some areas. This may be leading to greater localization of cannabis markets. It may also be responsible for the increase in the proportion of cannabis users in treatment populations at the international level. Assessing the extent and impact of this trend, however, is hampered both by a lack of international standards on issues such as terminology and by unanswered research questions. In order to arrive at accurate global estimates of the extent of production, there is a need for more scientific data on cannabis yields. On the demand side, more information is required on the question of cannabis dosage and volumes used by both occasional and regular users. Cannabis is not a uniform drug: the impact of using cannabis of differing potencies and chemical compositions needs to be researched. While issues concerning cannabis have been evaluated many times in the past, it remains a highly adaptable plant and, consequently, a dynamic drug, requiring constant reassessment.

A Metabolomic Approach Applied to a Liquid Chromatography Coupled to High-Resolution Tandem Mass Spectrometry Method (HPLC-ESI-HRMS/MS): Towards the Comprehensive Evaluation of the Chemical Composition of Cannabis Medicinal Extracts.

PubMed

Citti, Cinzia; Battisti, Umberto Maria; Braghiroli, Daniela; Ciccarella, Giuseppe; Schmid, Martin; Vandelli, Maria Angela; Cannazza, Giuseppe

2018-03-01

Cannabis sativa L. is a powerful medicinal plant and its use has recently increased for the treatment of several pathologies. Nonetheless, side effects, like dizziness and hallucinations, and long-term effects concerning memory and cognition, can occur. Most alarming is the lack of a standardised procedure to extract medicinal cannabis. Indeed, each galenical preparation has an unknown chemical composition in terms of cannabinoids and other active principles that depends on the extraction procedure. This study aims to highlight the main differences in the chemical composition of Bediol® extracts when the extraction is carried out with either ethyl alcohol or olive oil for various times (0, 60, 120 and 180 min for ethyl alcohol, and 0, 60, 90 and 120 min for olive oil). Cannabis medicinal extracts (CMEs) were analysed by liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS) using an untargeted metabolomics approach. The data sets were processed by unsupervised multivariate analysis. Our results suggested that the main difference lies in the ratio of acid to decarboxylated cannabinoids, which dramatically influences the pharmacological activity of CMEs. Minor cannabinoids, alkaloids, and amino acids contributing to this difference are also discussed. The main cannabinoids were quantified in each extract applying a recently validated LC-MS and LC-UV method. Notwithstanding the use of a standardised starting plant material, great changes are caused by different extraction procedures. The metabolomics approach is a useful tool for the evaluation of the chemical composition of cannabis extracts. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Cannabis and creativity: highly potent cannabis impairs divergent thinking in regular cannabis users.

PubMed

Kowal, Mikael A; Hazekamp, Arno; Colzato, Lorenza S; van Steenbergen, Henk; van der Wee, Nic J A; Durieux, Jeffrey; Manai, Meriem; Hommel, Bernhard

2015-03-01

Cannabis users often claim that cannabis has the potential to enhance their creativity. Research suggests that aspects of creative performance might be improved when intoxicated with cannabis; however, the evidence is not conclusive. The aim of this study was to investigate the acute effects of cannabis on creativity. We examined the effects of administering a low (5.5 mg delta-9-tetrahydrocannabinol [THC]) or high (22 mg THC) dose of vaporized cannabis vs. placebo on creativity tasks tapping into divergent (Alternate Uses Task) and convergent (Remote Associates Task) thinking, in a population of regular cannabis users. The study used a randomized, double-blind, between-groups design. Participants in the high-dose group (n = 18) displayed significantly worse performance on the divergent thinking task, compared to individuals in both the low-dose (n = 18) and placebo (n = 18) groups. The findings suggest that cannabis with low potency does not have any impact on creativity, while highly potent cannabis actually impairs divergent thinking.

Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol.

PubMed

Smeriglio, Antonella; Giofrè, Salvatore V; Galati, Enza M; Monforte, Maria T; Cicero, Nicola; D'Angelo, Valeria; Grassi, Gianpaolo; Circosta, Clara

2018-02-07

Aldose reductase (ALR2) is a key enzyme involved in diabetic complications and the search for new aldose reductase inhibitors (ARIs) is currently very important. The synthetic ARIs are often associated with deleterious side effects and medicinal and edible plants, containing compounds with aldose reductase inhibitory activity, could be useful for prevention and therapy of diabetic complications. Non-psychotropic phytocannabinoids exert multiple pharmacological effects with therapeutic potential in many diseases such as inflammation, cancer, diabetes. Here, we have investigated the inhibitory effects of extracts and their fractions from two Cannabis sativa L. chemotypes with high content of cannabidiol (CBD)/cannabidiolic acid (CBDA) and cannabigerol (CBG)/cannabigerolic acid (CBGA), respectively, on human recombinant and pig kidney aldose reductase activity in vitro. A molecular docking study was performed to evaluate the interaction of these cannabinoids with the active site of ALR2 compared to known ARIs. The extracts showed significant dose-dependent aldose reductase inhibitory activity (>70%) and higher than fractions. The inhibitory activity of the fractions was greater for acidic cannabinoid-rich fractions. Comparative molecular docking results have shown a higher stability of the ALR2-cannabinoid acids complex than the other inhibitors. The extracts of Cannabis with high content of non-psychotropic cannabinoids CBD/CBDA or CBG/CBGA significantly inhibit aldose reductase activity. These results may have some relevance for the possible use of C. sativa chemotypes based preparations as aldose reductase inhibitors. Copyright © 2018 Elsevier B.V. All rights reserved.

Ammonia release from heated 'street' cannabis leaf and its potential toxic effects on cannabis users.

PubMed

Bloor, Roger N; Wang, Tianshu S; Spanel, Patrik; Smith, David

2008-10-01

To use selected ion flow tube mass spectrometry (SIFT-MS) to analyse the molecular species emitted by heated 'street' cannabis plant material, especially targeting ammonia. Samples of 'street' cannabis leaf, held under a UK Home Office licence, were prepared by finely chopping and mixing the material. The samples were then heated in commercially available devices. The air containing the released gaseous compounds was sampled into the SIFT-MS instrument for analysis. Smoke from standard 3% National Institute on Drug Abuse (NIDA) cannabis cigarettes was also analysed. For 'street' cannabis, ammonia was present in the air samples from the devices at levels approaching 200 parts per million (p.p.m.). This is compared with peak levels of 10 p.p.m. using NIDA samples of known provenance and tetrahydrocannabinol content (3%). Several other compounds were present at lower levels, including acetaldehyde, methanol, acetone, acetic acid and uncharacterized terpenes. Awareness of the risks of inhaling the smoke directly from burning cannabis has led to the development of a number of alternative methods of delivery, which are claimed to be safer than direct smoking. Ammonia at toxic levels is produced from heating 'street' cannabis in these commercially available devices. Thus, the use of these devices to deliver 'street' cannabis is now open to question and further research is needed to investigate their safety.

Association between increased EEG signal complexity and cannabis dependence.

PubMed

Laprevote, Vincent; Bon, Laura; Krieg, Julien; Schwitzer, Thomas; Bourion-Bedes, Stéphanie; Maillard, Louis; Schwan, Raymund

2017-12-01

Both acute and regular cannabis use affects the functioning of the brain. While several studies have demonstrated that regular cannabis use can impair the capacity to synchronize neural assemblies during specific tasks, less is known about spontaneous brain activity. This can be explored by measuring EEG complexity, which reflects the spontaneous variability of human brain activity. A recent study has shown that acute cannabis use can affect that complexity. Since the characteristics of cannabis use can affect the impact on brain functioning, this study sets out to measure EEG complexity in regular cannabis users with or without dependence, in comparison with healthy controls. We recruited 26 healthy controls, 25 cannabis users without cannabis dependence and 14 cannabis users with cannabis dependence, based on DSM IV TR criteria. The EEG signal was extracted from at least 250 epochs of the 500ms pre-stimulation phase during a visual evoked potential paradigm. Brain complexity was estimated using Lempel-Ziv Complexity (LZC), which was compared across groups by non-parametric Kruskall-Wallis ANOVA. The analysis revealed a significant difference between the groups, with higher LZC in participants with cannabis dependence than in non-dependent cannabis users. There was no specific localization of this effect across electrodes. We showed that cannabis dependence is associated to an increased spontaneous brain complexity in regular users. This result is in line with previous results in acute cannabis users. It may reflect increased randomness of neural activity in cannabis dependence. Future studies should explore whether this effect is permanent or diminishes with cannabis cessation. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Effects of cannabis and tobacco on the enzymes of alcohol metabolism in the rat.

PubMed

Marselos, M; Vasiliou, V; Malamas, M; Alikaridis, F; Kefalas, T

1991-01-01

The effects of cannabis and tobacco on the enzymes of ethanol metabolism were studied in the Wistar rat. The activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (AlDH) were measured in the liver and the brain, after treatment with an extract of cannabis resin, with an extract of tobacco leaves, or with nicotine. A condensate of cannabis resin extract was collected in a smoking machine, using a tobacco cigarette as the vehicle. Unsmoked or smoked cannabis extracts were dissolved in olive oil and were given i.p. (twice daily, for 7 days). In both cases, a similar dose level was used in terms of starting material (raw cannabis resin), estimated at about 100 mg/kg body weight. Control animals were treated either with olive oil, or with the same amount of smoked condensate obtained from a reference cigarette. Nicotine was dissolved in olive oil and it was given i.p. (10 micrograms/kg, twice daily for 7 days). An extract of unsmoked tobacco was dissolved in olive oil and was given with the same schedule, at a dose which was estimated to correspond to about 10 micrograms nicotine/kg b.w. All groups of animals received an additional i.p. injection on day 8, one hour before sacrifice. Our results showed that unsmoked cannabis inhibited the hepatic activities of the microchondrial AlDH (low-Km and high-Km), the hepatic low-Km cytosolic AlDH (p less than 0.001), and the low-Km mitochondrial AlDH of the brain (p less than 0.001). Administration of smoked cannabis to the animals inhibited the hepatic mitochondrial low-Km AlDH (p less than 0.001), but it did not influence the brain enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Prescribing smoked cannabis for chronic noncancer pain

PubMed Central

Kahan, Meldon; Srivastava, Anita; Spithoff, Sheryl; Bromley, Lisa

2014-01-01

Objective To offer preliminary guidance on prescribing smoked cannabis for chronic pain before the release of formal guidelines. Quality of evidence We reviewed the literature on the analgesic effectiveness of smoked cannabis and the harms of medical and recreational cannabis use. We developed recommendations on indications, contraindications, precautions, and dosing of smoked cannabis, and categorized the recommendations based on levels of evidence. Evidence is mostly level II (well conducted observational studies) and III (expert opinion). Main message Smoked cannabis might be indicated for patients with severe neuropathic pain conditions who have not responded to adequate trials of pharmaceutical cannabinoids and standard analgesics (level II evidence). Smoked cannabis is contraindicated in patients who are 25 years of age or younger (level II evidence); who have a current, past, or strong family history of psychosis (level II evidence); who have a current or past cannabis use disorder (level III evidence); who have a current substance use disorder (level III evidence); who have cardiovascular or respiratory disease (level III evidence); or who are pregnant or planning to become pregnant (level II evidence). It should be used with caution in patients who smoke tobacco (level II evidence), who are at increased risk of cardiovascular disease (level III evidence), who have anxiety or mood disorders (level II evidence), or who are taking higher doses of opioids or benzodiazepines (level III evidence). Cannabis users should be advised not to drive for at least 3 to 4 hours after smoking, for at least 6 hours after oral ingestion, and for at least 8 hours if they experience a subjective “high” (level II evidence). The maximum recommended dose is 1 inhalation 4 times per day (approximately 400 mg per day) of dried cannabis containing 9% delta-9-tetrahydrocannabinol (level III evidence). Physicians should avoid referring patients to “cannabinoid” clinics (level

Is the clinical use of cannabis by oncology patients advisable?

PubMed

Bar-Sela, Gil; Avisar, Adva; Batash, Ron; Schaffer, Moshe

2014-06-01

The use of the cannabis plant for various medical indications by cancer patients has been rising significantly in the past few years in several European countries, the US and Israel. The increase in use comes from public demand for the most part, and not due to a scientific basis. Cannabis chemistry is complex, and the isolation and extraction of the active ingredient remain difficult. The active agent in cannabis is unique among psychoactive plant materials, as it contains no nitrogen and, thus, is not an alkaloid. Alongside inconclusive evidence of increased risks of lung and head and neck cancers from prolonged smoking of the plant produce, laboratory evidence of the anti-cancer effects of plant components exists, but with no clinical research in this direction. The beneficial effects of treatment with the plant, or treatment with medicine produced from its components, are related to symptoms of the disease: pain, nausea and vomiting, loss of appetite and weight loss. The clinical evidence of the efficacy of cannabis for these indications is only partial. However, recent scientific data from studies with THC and cannabidiol combinations report the first clinical indication of cancer-related pain relief. The difficulties of performing research into products that are not medicinal, such as cannabis, have not allowed a true study of the cannabis plant extract although, from the public point of view, such studies are greatly desirable.

Cannabis and schizophrenia

PubMed Central

Rathbone, John; Variend, Hannele; Mehta, Hetal

2014-01-01

Background Many people with schizophrenia use cannabis and its effects on the illness are unclear. Objectives To evaluate the effects of cannabis use on people with schizophrenia and schizophrenia-like illnesses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. Selection criteria We included all randomised trials involving cannabinoids and people with schizophrenia or schizophrenia-like illnesses. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed effects model. We calculated the numbers needed to treat/harm (NNT/NNH). For continuous data, we calculated weighted mean differences (WMD) again based on a fixed effects model. Main results We identified one randomised trial. No significant differences were found between the Cannabis and Psychosis Therapy (CAP) intervention group and the Psychoeducaton (PE) intervention for use of cannabis at three months assessment (n=47, RR 1.04 CI 0.6 to 1.7). BPRS-extended scale scores at three months assessment (n=47, WMD −3.60 CI −12.8 to 5.6) and nine months assessment (n=47, WMD 0.80 CI −7.5 to 9.1) were non-significant between CAP and PE. We found no significant improvement in social functioning in the CAP group compared with PE (at 3 months, n=47, WMD −0.80 CI −10 to 8.4) and (at 9 months, n=47, WMD −4.70 CI −14.5 to 5.1). Authors’ conclusions At present, there is insufficient evidence to support or refute the use of cannabis/cannabinoid compounds for people suffering with schizophrenia. This review highlights the need for well designed, conducted and reported clinical trials to address the potential effects of cannabis based compounds for people with schizophrenia. PMID:18646115

Cannabis Epidemiology: A Selective Review

PubMed Central

Anthony, James C.; Lopez-Quintero, Catalina; Alshaarawy, Omayma

2017-01-01

Background Globally, the most widely used set of compounds among the internationally regulated drugs is cannabis. Objective To review evidence from epidemiological research on cannabis, organized in relation to this field’s five main rubrics: quantity, location, causes, mechanisms, and prevention/control. Method The review covers a selection of evidence from standardized population surveys, official statistics, and governmental reports, as well as published articles and books identified via MEDLINE, Web of Science, and Google Scholar as of July 2016. Results In relation to quantity, an estimated 3% to 5% of the world population is thought to have tried a cannabis product, with at least one fairly recent use, mainly extra-medical and outside boundaries of prescribed use. Among cannabis users in the United States, roughly one in 7–8 has engaged in medical marijuana use. In relation to location, prevalence proportions reveal important variations across countries and between subgroups within countries. Regarding causes and mechanisms of starting to use cannabis, there is no compelling integrative and replicable conceptual model or theoretical formulation. Most studies of mechanisms have focused upon a ‘gateway sequence’ and person-to-person diffusion, with some recent work on disability-adjusted life years. A brief review of cannabis use consequences, as well as prevention and control strategies is also provided. Conclusion At present, we know much about the frequency and occurrence of cannabis use, with too little replicable definitive evidence with respect to the other main rubrics. Given a changing regulatory environment for cannabis products, new institutions such as an independent International Cannabis Products Safety Commission may be required to produce evidence required to weigh benefits versus costs. It is not clear that government sponsored research will be sufficient to meet consumer demand for balanced points of view and truly definitive evidence

Cannabis Epidemiology: A Selective Review.

PubMed

Anthony, James C; Lopez-Quintero, Catalina; Alshaarawy, Omayma

2017-01-04

Globally, the most widely used set of compounds among the internationally regulated drugs is cannabis. To review evidence from epidemiological research on cannabis, organized in relation to this field's five main rubrics: quantity, location, causes, mechanisms, and prevention/ control. The review covers a selection of evidence from standardized population surveys, official statistics, and governmental reports, as well as published articles and books identified via MEDLINE, Web of Science, and Google Scholar as of July 2016. In relation to quantity, an estimated 3% to 5% of the world population is thought to have tried a cannabis product, with at least one fairly recent use, mainly extra-medical and outside boundaries of prescribed use. Among cannabis users in the United States, roughly one in 7-8 has engaged in medical marijuana use. In relation to location, prevalence proportions reveal important variations across countries and between subgroups within countries. Regarding causes and mechanisms of starting to use cannabis, there is no compelling integrative and replicable conceptual model or theoretical formulation. Most studies of mechanisms have focused upon a 'gateway sequence' and person-to-person diffusion, with some recent work on disability-adjusted life years. A brief review of cannabis use consequences, as well as prevention and control strategies is also provided. At present, we know much about the frequency and occurrence of cannabis use, with too little replicable definitive evidence with respect to the other main rubrics. Given a changing regulatory environment for cannabis products, new institutions such as an independent International Cannabis Products Safety Commission may be required to produce evidence required to weigh benefits versus costs. It is not clear that governmentsponsored research will be sufficient to meet consumer demand for balanced points of view and truly definitive evidence. Copyright© Bentham Science Publishers; For any queries

Cannabis, pain, and sleep: lessons from therapeutic clinical trials of Sativex, a cannabis-based medicine.

PubMed

Russo, Ethan B; Guy, Geoffrey W; Robson, Philip J

2007-08-01

Cannabis sativa L. has been utilized for treatment of pain and sleep disorders since ancient times. This review examines modern studies on effects of Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on sleep. It goes on to report new information on the effects on sleep in the context of medical treatment of neuropathic pain and symptoms of multiple sclerosis, employing standardized oromucosal cannabis-based medicines containing primarily THC, CBD, or a 1 : 1 combination of the two (Sativex). Sleep-laboratory results indicate a mild activating effect of CBD, and slight residual sedation with THC-predominant extracts. Experience to date with Sativex in numerous Phase I-III studies in 2000 subjects with 1000 patient years of exposure demonstrate marked improvement in subjective sleep parameters in patients with a wide variety of pain conditions including multiple sclerosis, peripheral neuropathic pain, intractable cancer pain, and rheumatoid arthritis, with an acceptable adverse event profile. No tolerance to the benefit of Sativex on pain or sleep, nor need for dosage increases have been noted in safety extension studies of up to four years, wherein 40-50% of subjects attained good or very good sleep quality, a key source of disability in chronic pain syndromes that may contribute to patients' quality of life.

The effect of medical cannabis laws on juvenile cannabis use.

PubMed

Stolzenberg, Lisa; D'Alessio, Stewart J; Dariano, Dustin

2016-01-01

A number of states in the United States legally allow the use of cannabis as a medical therapy to treat an illness or to alleviate symptoms. Concern persists as to whether these types of laws are increasing juvenile recreational cannabis use. It is also plausible that medical cannabis laws engender an escalation of illicit non-cannabis drug use among juveniles because cannabis is frequently considered to be a gateway drug. This study uses longitudinal data drawn from the National Survey on Drug Use and Health for the 50 U.S. states and a cross-sectional pooled-time series research design to investigate the effect of medical cannabis laws on juvenile cannabis use and on juvenile non-cannabis illicit drug use. Our study period encompasses five measurement periods calibrated in two-year intervals (2002-2003 to 2010-2011). This research design is advantageous in that it affords us the ability not only to assess the effect of the implementation of medical cannabis laws on juvenile drug use, but also to consider other state-specific factors that may explain variation in drug use that cannot be accounted for using a single time series. Findings show that medical cannabis laws amplify recreational juvenile cannabis use. Other salient predictors of juvenile cannabis use at the state-level of analysis include perceived availability of cannabis, percent of juveniles skipping school, severity of perceived punishment for cannabis possession, alcohol consumption, percent of respondents with a father residing in household, and percent of families in the state receiving public assistance. There is little empirical evidence to support the view that medical cannabis laws affect juveniles' use of illicit non-cannabis drugs. Based on our findings, it seems reasonable to speculate that medical cannabis laws amplify juveniles' use of cannabis by allaying the social stigma associated with recreational cannabis use and by placating the fear that cannabis use could potentially result in a

Cannabis Use, Lung Cancer, and Related Issues.

PubMed

Jett, James; Stone, Emily; Warren, Graham; Cummings, K Michael

2018-04-01

The cannabis plant and its derivatives have been exploited for centuries for recreational and medicinal purposes, with millions of regular users around the world. The recreational use of cannabis is reflective of its neuropsychiatric effects, such as anxiolysis and euphoria. However, cannabis appears to have an emerging therapeutic role, especially in chronic disease and as an adjunct to cancer treatment. Increasing evidence supports cannabis in the management of chemotherapy-induced nausea and vomiting (CINV) and for pain management; however, studies are limited, particularly by difficulties associated with standardized dosing estimates and inability to accurately assess biologic activities of compounds in cannabis and derivative products. Smoking cannabis has not been proved to be a risk factor in the development of lung cancer, but the data are limited by small studies, misclassification due to self-reporting of use, small numbers of heavy cannabis smokers, and confounding of the risk associated with known causative agents for lung cancer (such as parallel chronic tobacco use). Cannabis and its biologically effective derivatives warrant additional research, ideally, controlled trials in which the cannabidiol and the delta-9-tetrahydrocabinol strength and use are controlled and documented. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Aerobic Exercise Training Reduces Cannabis Craving and Use in Non-Treatment Seeking Cannabis-Dependent Adults

PubMed Central

Buchowski, Maciej S.; Meade, Natalie N.; Charboneau, Evonne; Park, Sohee; Dietrich, Mary S.; Cowan, Ronald L.; Martin, Peter R.

2011-01-01

Background Cannabis dependence is a significant public health problem. Because there are no approved medications for this condition, treatment must rely on behavioral approaches empirically complemented by such lifestyle change as exercise. Aims To examine the effects of moderate aerobic exercise on cannabis craving and use in cannabis dependent adults under normal living conditions. Design Participants attended 10 supervised 30-min treadmill exercise sessions standardized using heart rate (HR) monitoring (60–70% HR reserve) over 2 weeks. Exercise sessions were conducted by exercise physiologists under medical oversight. Participants Sedentary or minimally active non-treatment seeking cannabis-dependent adults (n = 12, age 25±3 years, 8 females) met criteria for primary cannabis dependence using the Substance Abuse module of the Structured Clinical Interview for DSM-IV (SCID). Measurements Self-reported drug use was assessed for 1-week before, during, and 2-weeks after the study. Participants viewed visual cannabis cues before and after exercise in conjunction with assessment of subjective cannabis craving using the Marijuana Craving Questionnaire (MCQ-SF). Findings Daily cannabis use within the run-in period was 5.9 joints per day (SD = 3.1, range 1.8–10.9). Average cannabis use levels within the exercise (2.8 joints, SD = 1.6, range 0.9–5.4) and follow-up (4.1 joints, SD = 2.5, range 1.1–9.5) periods were lower than during the run-in period (both P<.005). Average MCQ factor scores for the pre- and post-exercise craving assessments were reduced for compulsivity (P  = .006), emotionality (P  = .002), expectancy (P  = .002), and purposefulness (P  = .002). Conclusions The findings of this pilot study warrant larger, adequately powered controlled trials to test the efficacy of prescribed moderate aerobic exercise as a component of cannabis dependence treatment. The neurobiological mechanisms that account for these beneficial

Qualitative and quantitative measurement of cannabinoids in cannabis using modified HPLC/DAD method.

PubMed

Patel, Bhupendra; Wene, Daniel; Fan, Zhihua Tina

2017-11-30

This study presents an accurate and high throughput method for the quantitative determination of various cannabinoids in cannabis plant material using high pressure liquid chromatography (HPLC) with a diode array detector (DAD). Sample extraction and chromatographic analysis conditions for the measurement of cannabinoids in the complex cannabis plant material matrix were optimized. The Agilent Poroshell 120 SB-C18 column provided high resolution for all target analytes with a short run time (10minutes) given the core shell technology. The aqueous buffer mobile phase was optimized with ammonium acetate at pH 4.75. The change in the mobile phase and the new column ensured a separation between cannabidiol (CBD and cannabigerol (CBG) along with cannabigerol and tetrahydrocannabinolic acid (THCA), which were not well separated by previous publications, improved buffering capacity, and provided analytical performance stability. Moreover, baseline drifting was significantly minimized by the use of a low concentration buffer solution (25mM ammonium acetate). In addition, evaporation and reconstitution of the sample residue with a methanol-organic pure (OP) water solution (65:35) significantly reduced the matrix interference. The modified extraction produced good recoveries (>91%) for each of the eight cannabinoids. The optimized method was validated for specificity, linearity, sensitivity, precision, accuracy, and stability. The combined relative standard deviation (%RSD) for intra-day and inter-day precision for all eight analytes varied from 2.5% to 5.2% and 0.28% to 5.5%, respectively. The %RSD for the repeatability study varied from 1.1% to 5.5%. The recoveries from spiked cannabis matrix samples were greater than 90% for all analytes, except delta-8-tetrahydrocannabinol (Δ 8 -THC), which was 80%. The recoveries varied from 81% to 107% with a precision of 0.7-8.1%RSD. Delta-9-tetrahydrocannabinol (Δ 9 -THC) in all of the cannabis samples (n=635) was less than 10

Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial.

PubMed

Allsop, David J; Copeland, Jan; Lintzeris, Nicholas; Dunlop, Adrian J; Montebello, Mark; Sadler, Craig; Rivas, Gonzalo R; Holland, Rohan M; Muhleisen, Peter; Norberg, Melissa M; Booth, Jessica; McGregor, Iain S

2014-03-01

There are no medications approved for treating cannabis dependence or withdrawal. The cannabis extract nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal. To evaluate the safety and efficacy of nabiximols in treating cannabis withdrawal. A 2-site, double-blind randomized clinical inpatient trial with a 28-day follow-up was conducted in New South Wales, Australia. Participants included 51 DSM-IV-TR cannabis-dependent treatment seekers. A 6-day regimen of nabiximols (maximum daily dose, 86.4 mg of Δ9-tetrahydrocannabinol and 80 mg of cannabidiol) or placebo with standardized psychosocial interventions during a 9-day admission. Severity of cannabis withdrawal and cravings (Cannabis Withdrawal Scale), retention in withdrawal treatment, and adverse events. Secondary outcomes include postwithdrawal cannabis use, health outcomes, and psychosocial outcomes. Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo (F8,377.97 = 2.39; P = .01), including effects on withdrawal-related irritability, depression, and cannabis cravings. Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbance, anxiety, appetite loss, physical symptoms, and restlessness. Nabiximols patients remained in treatment longer during medication use (unadjusted hazard ratio, 3.66 [95% CI, 1.18-11.37]; P = .02), with 2.84 the number needed to treat to achieve successful retention in treatment. Participants could not reliably differentiate between nabiximols and placebo treatment (χ21 = 0.79; P = .67), and those receiving nabiximols did not report greater intoxication (F1,6 = 0.22; P = .97). The number (F1,50 = 0.3; P = .59) and severity (F1,50 = 2.69; P = .10) of adverse events did not differ significantly between groups. Both groups showed reduced cannabis use at follow-up, with no advantage of

Differential effects of THC- or CBD-rich cannabis extracts on working memory in rats.

PubMed

Fadda, Paola; Robinson, Lianne; Fratta, Walter; Pertwee, Roger G; Riedel, Gernot

2004-12-01

Cannabinoid receptors in the brain (CB(1)) take part in modulation of learning, and are particularly important for working and short-term memory. Here, we employed a delayed-matching-to-place (DMTP) task in the open-field water maze and examined the effects of cannabis plant extracts rich in either Delta(9)-tetrahydrocannabinol (Delta(9)-THC), or rich in cannabidiol (CBD), on spatial working and short-term memory formation in rats. Delta(9)-THC-rich extracts impaired performance in the memory trial (trial 2) of the DMTP task in a dose-dependent but delay-independent manner. Deficits appeared at doses of 2 or 5 mg/kg (i.p.) at both 30 s and 4 h delays and were similar in severity compared with synthetic Delta(9)-THC. Despite considerable amounts of Delta(9)-THC present, CBD-rich extracts had no effect on spatial working/short-term memory, even at doses of up to 50 mg/kg. When given concomitantly, CBD-rich extracts did not reverse memory deficits of the additional Delta(9)-THC-rich extract. CBD-rich extracts also did not alter Delta(9)-THC-rich extract-induced catalepsy as revealed by the bar test. It appears that spatial working/short-term memory is not sensitive to CBD-rich extracts and that potentiation and antagonism of Delta(9)-THC-induced spatial memory deficits is dependent on the ratio between CBD and Delta(9)-THC.

Cannabis use expectancies mediate the relation between depressive symptoms and cannabis use among cannabis-dependent veterans.

PubMed

Farris, Samantha G; Zvolensky, Michael J; Boden, Matthew Tyler; Bonn-Miller, Marcel O

2014-01-01

The current study examined the cross-sectional associations between depressive symptoms and cannabis use, and the mediating role of positive and negative expectancies of cannabis use. Participants (n = 100) were cannabis-dependent veterans recruited as part of a larger self-guided cannabis quit study. Baseline (prequit) data were used. Depressive symptoms were assessed using the General Depression subscale of the Inventory of Depression and Anxiety Symptoms (IDAS), and cannabis use expectancies were assessed using the Marijuana Effect Expectancies Questionnaire. Quantity of cannabis use in the past 90 days was assessed with the Timeline Follow-Back. A parallel multiple mediation path analysis was conducted to simultaneously examine the effects of positive and negative expectancies as mediators of the relation between IDAS-Depression and prequit cannabis use. Results indicated that depressive symptoms were indirectly related to cannabis use through positive, but not negative, expectancies. This effect was unique to IDAS-Dysphoria symptoms. Depressive symptoms, particularly cognitive-affective symptom features, may be important to consider in better understanding positive cannabis effect expectancies among veterans in regard to cannabis use.

Medical use of cannabis and cannabinoids containing products - Regulations in Europe and North America.

PubMed

Abuhasira, Ran; Shbiro, Liat; Landschaft, Yuval

2018-03-01

In 1937, the United States of America criminalized the use of cannabis and as a result its use decreased rapidly. In recent decades, there is a growing interest in the wide range of medical uses of cannabis and its constituents; however, the laws and regulations are substantially different between countries. Laws differentiate between raw herbal cannabis, cannabis extracts, and cannabinoid-based medicines. Both the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) do not approve the use of herbal cannabis or its extracts. The FDA approved several cannabinoid-based medicines, so did 23 European countries and Canada. However, only four of the reviewed countries have fully authorized the medical use of herbal cannabis - Canada, Germany, Israel and the Netherlands, together with more than 50% of the states in the United States. Most of the regulators allow the physicians to decide what specific indications they will prescribe cannabis for, but some regulators dictate only specific indications. The aim of this article is to review the current (as of November 2017) regulations of medical cannabis use in Europe and North America. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Psychiatric Morbidity of Cannabis Abuse

PubMed Central

Sarkar, Jaydip; Murthy, Pratima; Singh, Swaran P

2003-01-01

The paper evaluates the hypothesis that cannabis abuse is associated with a broad range of psychiatric disorders in India, an area with relatively high prevalence of cannabis use. Retrospective case-note review of all cases with cannabis related diagnosis over a 11 -year period, for subjects presenting to a tertiary psychiatric hospital in southern India was carried out. Information pertaining to sociodemographic, personal, social, substance-use related, psychiatric and treatment histories, was gathered. Standardized diagnoses were made according to Diagnostic Criteria for Research of the World Health Organization, on the basis of information available. Cannabis abuse is associated with widespread psychiatric morbidity that spans the major categories of mental disorders under the ICD-10 system, although proportion of patients with psychotic disorders far outweighed those with non-psychotic disorders. Whilst paranoid psychoses were more prevalent, a significant number of patients with affective psychoses, particularly mania, was also noted. Besides being known as either the causative agent or a potent risk factor in cases of paranoid psychoses, cannabis appears to have similar capabilities with regard to affective psychoses, particularly in cases of mania. It is suggested that cannabis has the potential to act as a "life event stressor" amongst subjects vulnerable to develop affective psychoses and the possible aetiopathogenesis of such a finding is discussed. PMID:21206852

Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration.

PubMed

Karschner, Erin L; Darwin, W David; Goodwin, Robert S; Wright, Stephen; Huestis, Marilyn A

2011-01-01

Sativex(®), a cannabis extract oromucosal spray containing Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC's effects, but it is unclear if this is due to a pharmacokinetic and/or pharmacodynamic interaction. Cannabis smokers provided written informed consent to participate in this randomized, controlled, double-blind, double-dummy institutional review board-approved study. Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and 5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over 5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor- 9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS. Lower limits of quantification were ≤0.25 μg/L. Nine cannabis smokers completed all 5 dosing sessions. Significant differences (P < 0.05) in maximum plasma concentrations (C(max)) and areas under the curve from 0-10.5 h postdose (AUC(0→10.5)) for all analytes were found between low and high doses of synthetic THC and Sativex. There were no statistically significant differences in C(max), time to maximum concentration or in the AUC(0→10.5) between similar oral THC and Sativex doses. Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively. These data suggest that CBD modulation of THC's effects is not due to a pharmacokinetic interaction at these therapeutic doses.

Plasma Cannabinoid Pharmacokinetics following Controlled Oral Δ9-Tetrahydrocannabinol and Oromucosal Cannabis Extract Administration

PubMed Central

Karschner, Erin L.; Darwin, W. David; Goodwin, Robert S.; Wright, Stephen; Huestis, Marilyn A.

2013-01-01

BACKGROUND Sativex®, a cannabis extract oromucosal spray containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC’s effects, but it is unclear if this is due to a pharmacokinetic and/or pharmacodynamic interaction. METHODS Cannabis smokers provided written informed consent to participate in this randomized, controlled, double-blind, double-dummy institutional review board–approved study. Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and 5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over 5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS. Lower limits of quantification were ≤0.25 μg/L. RESULTS Nine cannabis smokers completed all 5 dosing sessions. Significant differences (P < 0.05) in maximum plasma concentrations (Cmax) and areas under the curve from 0–10.5 h postdose (AUC0→10.5) for all analytes were found between low and high doses of synthetic THC and Sativex. There were no statistically significant differences in Cmax, time to maximum concentration or in the AUC0→10.5 between similar oral THC and Sativex doses. Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively. CONCLUSION These data suggest that CBD modulation of THC’s effects is not due to a pharmacokinetic interaction at these therapeutic doses. PMID:21078841

Pharmacology and toxicology of Cannabis derivatives and endocannabinoid agonists.

PubMed

Gerra, Gilberto; Zaimovic, Amir; Gerra, Maria L; Ciccocioppo, Roberto; Cippitelli, Andrea; Serpelloni, Giovanni; Somaini, Lorenzo

2010-01-01

For centuries Cannabis sativa and cannabis extracts have been used in natural medicine. Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis. In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma. On the other hand the severe side effects and the high abuse liability of these agents represent a serious limitation in their medical use. In addition, diversion in the use of these active ingredients for recreational purpose is a concern. Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications. Likely, in the near future few of these new molecules will be available for clinical use. The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists.

Cannabis arteritis.

PubMed

El Omri, Naoual; Eljaoudi, Rachid; Mekouar, Fadwa; Jira, Mohammed; Sekkach, Youssef; Amezyane, Taoufik; Ghafir, Driss

2017-01-01

Cannabis is the most consumed psychoactive substance by young people. Chronic use of cannabis can lead to cannabis arteritis, which is a very rare peripheral vascular disease similar to Buerger's disease. It is affecting young adults, especially men, consuming cannabis. A 27-year old woman, with no particular past medical history except for long-term use of cannabis and tobacco developed a digital necrosis in the left hand. She denied using other illicit drugs. Doppler ultrasound examination of the upper limbs was unremarkable. Toxicological analysis revealed the presence of cannabis in both biological fluid and hair strand. Despite medical treatment, cessation of the cannabis and tobacco consumption and hyperbaric oxygen therapy, an amputation of necrotic parts was then required. This case shows the prolonged use of cannabis could be a risk factor for young adult arteritis. Faced with a rapidly progressive arteritis occurring in young adult, the physician should consider the history of use of cannabis. Hair analysis can be useful for confirmation of the chronic consumption of drugs.

Segmental hair analysis for 11-nor-Δ⁹-tetrahydrocannabinol-9-carboxylic acid and the patterns of cannabis use.

PubMed

Han, Eunyoung; Chung, Heesun; Song, Joon Myong

2012-04-01

Cannabis is the most widely abused drug in the world. The purpose of this study is to detect 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (THCCOOH) in segmental hair and to evaluate the patterns of cannabis use. We investigated the relationship between the concentrations of THCCOOH in hair and the self-reported use data and the route of administration. For this purpose, the hair samples were washed, digested with 1 mL of 1 M NaOH at 85°C for 30 min along with the internal standard, THCCOOH-d₃ (2.5 pg/mg) and extracted in 2 mL of n-hexane-ethyl acetate (9:1) twice after adding 1 mL of 0.1N sodium acetate buffer (pH = 4.5) and 200 µL of acetic acid. The organic extract was transferred and evaporated and the mixture was derivatized with 50 µL of pentafluoropropionic anhydride and 25 µL of pentafluoropropanol for 30 min at 70°C. Reconstituted final extract was injected into the gas chromatography-tandem mass spectrometer operating in the negative chemical ionization mode. In segmental hair analysis, the concentrations of THCCOOH decreased from the proximal to distal segments. The concentrations of THCCOOH in hair and the self-reported dose and frequency of administration from cannabis users were not well correlated because of the low accuracy and reliability of the self-reported data. However, this study provides preliminary information on the dose and frequency of administration among cannabis users in our country.

Evaluation of Cannabinoid and Terpenoid Content: Cannabis Flower Compared to Supercritical CO2 Concentrate.

PubMed

Sexton, Michelle; Shelton, Kyle; Haley, Pam; West, Mike

2018-03-01

A recent cannabis use survey revealed that 60% of cannabis users rely on smelling the flower to select their cannabis. Olfactory indicators in plants include volatile compounds, principally represented by the terpenoid fraction. Currently, medicinal- and adult-use cannabis is marketed in the United States with relatively little differentiation between products other than by a common name, association with a species type, and Δ-9 tetrahydrocannabinol/cannabidiol potency. Because of this practice, how terpenoid compositions may change during an extraction process is widely overlooked. Here we report on a comparative study of terpenoid and cannabinoid potencies of flower and supercritical fluid CO 2 (SC-CO 2 ) extract from six cannabis chemovars grown in Washington State. To enable this comparison, we employed a validated high-performance liquid chromatography/diode array detector methodology for quantification of seven cannabinoids and developed an internal gas chromatography-mass spectrometry method for quantification of 42 terpenes. The relative potencies of terpenoids and cannabinoids in flower versus concentrate were significantly different. Cannabinoid potency increased by factors of 3.2 for Δ-9 tetrahydrocannabinol and 4.0 for cannabidiol in concentrates compared to flower. Monoterpenes were lost in the extraction process; a ketone increased by 2.2; an ether by 2.7; monoterpene alcohols by 5.3, 7 and 9.4; and sesquiterpenes by 5.1, 4.2, 7.7, and 8.9. Our results demonstrate that the product of SC-CO 2 extraction may have a significantly different chemotypic fingerprint from that of cannabis flower. These results highlight the need for more complete characterization of cannabis and associated products, beyond cannabinoid content, in order to further understand health-related consequences of inhaling or ingesting concentrated forms. Georg Thieme Verlag KG Stuttgart · New York.

Quality of web-based information on cannabis addiction.

PubMed

Khazaal, Yasser; Chatton, Anne; Cochand, Sophie; Zullino, Daniele

2008-01-01

This study evaluated the quality of Web-based information on cannabis use and addiction and investigated particular content quality indicators. Three keywords ("cannabis addiction," "cannabis dependence," and "cannabis abuse") were entered into two popular World Wide Web search engines. Websites were assessed with a standardized proforma designed to rate sites on the basis of accountability, presentation, interactivity, readability, and content quality. "Health on the Net" (HON) quality label, and DISCERN scale scores were used to verify their efficiency as quality indicators. Of the 94 Websites identified, 57 were included. Most were commercial sites. Based on outcome measures, the overall quality of the sites turned out to be poor. A global score (the sum of accountability, interactivity, content quality and esthetic criteria) appeared as a good content quality indicator. While cannabis education Websites for patients are widespread, their global quality is poor. There is a need for better evidence-based information about cannabis use and addiction on the Web.

Attitudes of cannabis growers to regulation of cannabis cultivation under a non-prohibition cannabis model.

PubMed

Lenton, Simon; Frank, Vibeke A; Barratt, Monica J; Dahl, Helle Vibeke; Potter, Gary R

2015-03-01

How cannabis cultivation is dealt with under various examples of cannabis legalization or regulation is an important consideration in design of such schemes. This study aimed to (i) investigate support among current or recent cannabis growers, for various potential policy options for cannabis cultivation if prohibition were repealed, and (ii) explore the support for these options across countries, scale of growing operations, demographics, drug use and cannabis supply involvement variables. This study utilized data from the online web survey of largely 'small-scale' cannabis cultivators, aged 18yrs and over, in eleven countries conducted by the Global Cannabis Cultivation Research Consortium (GCCRC). Data from 1722 current and recent cannabis growers in Australia, Denmark and the UK, who were all asked about policy, were included in the analysis. It investigated support for various frameworks for cultivation: (no regulation (free market); adult only; growing licenses; restrictions on plant numbers; licensed business-only sale; approved commercial growing; etc.). Among current growers, support for these options were compared across countries, across scale of growing operations, and by demographics, drug use and crime variables. Although there were some between country differences in support for the various policy options, what was striking was the similarity of the proportions for each of the eight most popular policy options. Among current growers, many of these positions were predicted by demographic, drug use and cannabis growing variables which were conceptually congruent with these positions. The results have relevance for the provisions regarding cannabis cultivation in the design of new non-prohibitionist models of cannabis which are increasingly under consideration. It should be of interest to policy makers, drug policy researchers, law enforcement and cannabis cultivators. Copyright © 2014 Elsevier B.V. All rights reserved.

Executive function deficits in short-term abstinent cannabis users.

PubMed

McHale, Sue; Hunt, Nigel

2008-07-01

Few cognitive tasks are adequately sensitive to show the small decrements in performance in abstinent chronic cannabis users. In this series of three experiments we set out to demonstrate a variety of tasks that are sufficiently sensitive to show differences in visual memory, verbal memory, everyday memory and executive function between controls and cannabis users. A series of three studies explored cognitive function deficits in cannabis users (phonemic verbal fluency, visual recognition and immediate and delayed recall, and prospective memory) in short-term abstinent cannabis users. Participants were selected using snowball sampling, with cannabis users being compared to a standard control group and a tobacco-use control group. The cannabis users, compared to both control groups, had deficits on verbal fluency, visual recognition, delayed visual recall, and short- and long-interval prospective memory. There were no differences for immediate visual recall. These findings suggest that cannabis use leads to impaired executive function. Further research needs to explore the longer term impact of cannabis use. Copyright 2008 John Wiley & Sons, Ltd.

Cannabis Guidelines
.

PubMed

Kennedy Sheldon, Lisa

2017-08-01

Cannabis has been used for centuries in the treatment of medical conditions. Cannabis has been recommended for appetite, anxiety, depression, sleep, and migraines. However, the stigma associated with cannabis as a recreational drug has created challenges to the legitimacy and social acceptance of cannabis for medical purposes in the United States.

Benefits and Harms of Plant-Based Cannabis for Posttraumatic Stress Disorder: A Systematic Review.

PubMed

O'Neil, Maya E; Nugent, Shannon M; Morasco, Benjamin J; Freeman, Michele; Low, Allison; Kondo, Karli; Zakher, Bernadette; Elven, Camille; Motu'apuaka, Makalapua; Paynter, Robin; Kansagara, Devan

2017-09-05

Cannabis is available from medical dispensaries for treating posttraumatic stress disorder (PTSD) in many states of the union, yet its efficacy in treating PTSD symptoms remains uncertain. To identify ongoing studies and review existing evidence regarding the benefits and harms of plant-based cannabis preparations in treating PTSD in adults. MEDLINE, the Cochrane Library, and other sources from database inception to March 2017. English-language systematic reviews, trials, and observational studies with a control group that reported PTSD symptoms and adverse effects of plant-based cannabis use in adults with PTSD. Study data extracted by 1 investigator was checked by a second reviewer; 2 reviewers independently assessed study quality, and the investigator group graded the overall strength of evidence by using standard criteria. Two systematic reviews, 3 observational studies, and no randomized trials were found. The systematic reviews reported insufficient evidence to draw conclusions about benefits and harms. The observational studies found that compared with nonuse, cannabis did not reduce PTSD symptoms. Studies had medium and high risk of bias, and overall evidence was judged insufficient. Two randomized trials and 6 other studies examining outcomes of cannabis use in patients with PTSD are ongoing and are expected to be completed within 3 years. Very scant evidence with medium to high risk of bias. Evidence is insufficient to draw conclusions about the benefits and harms of plant-based cannabis preparations in patients with PTSD, but several ongoing studies may soon provide important results. U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative. (PROSPERO: CRD42016033623).

Longitudinal study of hippocampal volumes in heavy cannabis users.

PubMed

Koenders, L; Lorenzetti, V; de Haan, L; Suo, C; Vingerhoets, Wam; van den Brink, W; Wiers, R W; Meijer, C J; Machielsen, Mwj; Goudriaan, A E; Veltman, D J; Yücel, M; Cousijn, J

2017-08-01

Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippocampus in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippocampal volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes. Twenty heavy cannabis users (mean age 21 years, range 18-24 years) and 23 matched non-cannabis using healthy controls were submitted to a comprehensive psychological assessment and magnetic resonance imaging scan at baseline and at follow-up (average of 39 months post-baseline; standard deviation=2.4). Cannabis users started smoking around 16 years and smoked on average five days per week. A novel aspect of the current study is that hippocampal volume estimates were obtained from manual tracing the hippocampus on T1-weighted anatomical magnetic resonance imaging scans, using a previously validated protocol. Compared to controls, cannabis users did not show hippocampal volume alterations at either baseline or follow-up. Hippocampal volumes increased over time in both cannabis users and controls, following similar trajectories of increase. Cannabis dose and age of onset of cannabis use did not affect hippocampal volumes. Continued heavy cannabis use did not affect hippocampal neuroanatomical changes in early adulthood. This contrasts with prior evidence on alterations in this region in samples of older adult cannabis users. In young adults using cannabis at this level, cannabis use may not be heavy enough to affect hippocampal neuroanatomy.

Longitudinal study of hippocampal volumes in heavy cannabis users

PubMed Central

Koenders, L; Lorenzetti, V; de Haan, L; Suo, C; Vingerhoets, WAM; van den Brink, W; Wiers, RW; Meijer, CJ; Machielsen, MWJ; Goudriaan, AE; Veltman, DJ; Yücel, M; Cousijn, J

2017-01-01

Background: Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippocampus in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippocampal volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes. Methods: Twenty heavy cannabis users (mean age 21 years, range 18–24 years) and 23 matched non-cannabis using healthy controls were submitted to a comprehensive psychological assessment and magnetic resonance imaging scan at baseline and at follow-up (average of 39 months post-baseline; standard deviation=2.4). Cannabis users started smoking around 16 years and smoked on average five days per week. A novel aspect of the current study is that hippocampal volume estimates were obtained from manual tracing the hippocampus on T1-weighted anatomical magnetic resonance imaging scans, using a previously validated protocol. Results: Compared to controls, cannabis users did not show hippocampal volume alterations at either baseline or follow-up. Hippocampal volumes increased over time in both cannabis users and controls, following similar trajectories of increase. Cannabis dose and age of onset of cannabis use did not affect hippocampal volumes. Conclusions: Continued heavy cannabis use did not affect hippocampal neuroanatomical changes in early adulthood. This contrasts with prior evidence on alterations in this region in samples of older adult cannabis users. In young adults using cannabis at this level, cannabis use may not be heavy enough to affect hippocampal neuroanatomy. PMID:28741422

Prescribing medical cannabis in Canada: Are we being too cautious?

PubMed

Lake, Stephanie; Kerr, Thomas; Montaner, Julio

2015-04-30

There has been much recent discussion and debate surrounding cannabis in Canada, including the prescribing of medical cannabis for therapeutic purposes. Certain commentators - including the Canadian Medical Association (CMA) - have denounced the prescribing of cannabis for medical purposes due to a perceived lack of evidence related to the drug's efficacy, harms, and mechanism of action. In this commentary, we present arguments in favour of prescribing medical cannabis in Canada. We believe the anti-cannabis position taken by CMA and other commentators is not entirely evidence-based. Using the example of neuropathic pain, we present and summarize the clinical evidence surrounding smoked or vapourized cannabis, including recent evidence pertaining to the effectiveness of cannabis in comparison to existing standard pharmacotherapies for neuropathy. Further, we outline how the concerns expressed regarding cannabis' mechanism of action are inconsistent with current decision-making processes related to the prescribing of many common pharmaceuticals. Finally, we discuss potential secondary public health benefits of prescribing cannabis for pain-related disorders in Canada and North America.

Cannabis-induced psychosis associated with high potency "wax dabs".

PubMed

Pierre, Joseph M; Gandal, Michael; Son, Maya

2016-04-01

With mounting evidence that the risk of cannabis-induced psychosis may be related to both dose and potency of tetrahydrocannbinol (THC), increasing reports of psychosis associated with cannabinoids containing greater amounts of THC are anticipated. We report two cases of emergent psychosis after using a concentrated THC extract known as cannabis "wax," "oil," or "dabs" raising serious concerns about its psychotic liability. Although "dabbing" with cannabis wax is becoming increasingly popular in the US for both recreational and "medicinal" intentions, our cases raise serious concerns about its psychotic liability and highlight the importance of understanding this risk by physicians recommending cannabinoids for purported medicinal purposes. Published by Elsevier B.V.

Effect of Ruta graveolens and Cannabis sativa alcoholic extract on spermatogenesis in the adult wistar male rats.

PubMed

Sailani, M R; Moeini, H

2007-07-01

The present study was undertaken to evaluate the effects of alcohol extracts of Ruta graveolens and Cannabis sativa that were used traditionally in medieval Persian medicine as male contraceptive drugs, on spermatogenesis in the adult male rats. Ethanol extracts of these plants were obtained by the maceration method. The male rats were injected intraperitionaly with C. sativa and R. graveolens 5% ethanol extracts at dose of 20 mg/day for 20 consecutive days, respectively. Twenty-four hours after the last treatment, testicular function was assessed by epididymal sperm count. The statistical results showed that the ethanol extracts of these plants reduced the number of sperms significantly (P=0.00) in the treatment groups in comparison to the control group. The results also showed that the group, treated by extract of R. graveolens reduced spermatogenesis more than the group treated by extracts of C. sativa. The present study demonstrated the spermatogenesis reducing properties of the ethanol extracts of R. graveolens and C. sativa in the adult male wistar rats but more studies are necessary to reveal the mechanism of action that is involved in spermatogenesis.

[MEDICAL CANNABIS].

PubMed

Naftali, Timna

2016-02-01

The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea and inflammation. Current research is inspecting the use of cannabis for many diseases, including multiple sclerosis, epilepsy, dystonia, and chronic pain. In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and:pain and diarrhea in Crohn's disease. Despite their therapeutic potential, cannabinoids are not free of side effects including psychosis, anxiety, paranoia, dependence and abuse. Controlled clinical studies investigating the therapeutic potential of cannabis are few and small, whereas pressure for expanding cannabis use is increasing. Currently, as long as cannabis is classified as an illicit drug and until further controlled studies are performed, the use of medical cannabis should be limited to patients who failed conventional better established treatment.

Distance to Cannabis Shops and Age of Onset of Cannabis Use.

PubMed

Palali, Ali; van Ours, Jan C

2015-11-01

In the Netherlands, cannabis use is quasi-legalized. Small quantities of cannabis can be bought in cannabis shops. We investigate how the distance to the nearest cannabis shop affects the age of onset of cannabis use. We use a mixed proportional hazard rate framework to take account of observable as well as unobservable characteristics that influence the uptake of cannabis. We find that distance matters. Individuals who grow up within 20 km of a cannabis shop have a lower age of onset. Copyright © 2014 John Wiley & Sons, Ltd.

Pharmacotherapies for cannabis dependence

PubMed Central

Marshall, Kushani; Gowing, Linda; Ali, Robert; Le Foll, Bernard

2015-01-01

Background Cannabis is the most prevalent illicit drug in the world. Demand for treatment of cannabis use disorders is increasing. There are currently no pharmacotherapies approved for treatment of cannabis use disorders. Objectives To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or supportive care for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (to 4 March 2014), MEDLINE (to week 3 February 2014), EMBASE (to 3 March 2014) and PsycINFO (to week 4 February 2014). We also searched reference lists of articles, electronic sources of ongoing trials and conference proceedings, and contacted selected researchers active in the area. Selection criteria Randomised and quasi-randomised controlled trials involving the use of medications to reduce the symptoms and signs of cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in participants diagnosed as cannabis dependent or who were likely to be dependent. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two review authors assessed studies for inclusion and extracted data. All review authors confirmed the inclusion decisions and the overall process. Main results We included 14 randomised controlled trials involving 958 participants. For 10 studies the average age was 33 years; two studies targeted young people; and age data were not available for two studies. Approximately 80% of study participants were male. The studies were at low risk of selection, performance, detection and selective outcome reporting bias. Three studies were at risk of attrition bias. All studies involved comparison of active medication and placebo. The medications included preparations containing

Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes

PubMed Central

De Petrocellis, Luciano; Ligresti, Alessia; Moriello, Aniello Schiano; Allarà, Marco; Bisogno, Tiziana; Petrosino, Stefania; Stott, Colin G; Di Marzo, Vincenzo

2011-01-01

BACKGROUND AND PURPOSE Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) interact with transient receptor potential (TRP) channels and enzymes of the endocannabinoid system. EXPERIMENTAL APPROACH The effects of 11 pure cannabinoids and botanical extracts [botanical drug substance (BDS)] from Cannabis varieties selected to contain a more abundant cannabinoid, on TRPV1, TRPV2, TRPM8, TRPA1, human recombinant diacylglycerol lipase α (DAGLα), rat brain fatty acid amide hydrolase (FAAH), COS cell monoacylglycerol lipase (MAGL), human recombinant N-acylethanolamine acid amide hydrolase (NAAA) and anandamide cellular uptake (ACU) by RBL-2H3 cells, were studied using fluorescence-based calcium assays in transfected cells and radiolabelled substrate-based enzymatic assays. Cannabinol (CBN), cannabichromene (CBC), the acids (CBDA, CBGA, THCA) and propyl homologues (CBDV, CBGV, THCV) of CBD, cannabigerol (CBG) and THC, and tetrahydrocannabivarin acid (THCVA) were also tested. KEY RESULTS CBD, CBG, CBGV and THCV stimulated and desensitized human TRPV1. CBC, CBD and CBN were potent rat TRPA1 agonists and desensitizers, but THCV-BDS was the most potent compound at this target. CBG-BDS and THCV-BDS were the most potent rat TRPM8 antagonists. All non-acid cannabinoids, except CBC and CBN, potently activated and desensitized rat TRPV2. CBDV and all the acids inhibited DAGLα. Some BDS, but not the pure compounds, inhibited MAGL. CBD was the only compound to inhibit FAAH, whereas the BDS of CBC > CBG > CBGV inhibited NAAA. CBC = CBG > CBD inhibited ACU, as did the BDS of THCVA, CBGV, CBDA and THCA, but the latter extracts were more potent inhibitors. CONCLUSIONS AND IMPLICATIONS These results are relevant to the analgesic, anti-inflammatory and anti-cancer effects of cannabinoids and Cannabis extracts. LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011

Agricultural innovations in Morocco's cannabis industry.

PubMed

Chouvy, Pierre-Arnaud; Macfarlane, Jennifer

2018-06-06

Cannabis cultivation in Morocco's mountainous Rif region is undergoing its most profound development since mass production of hashish began in the early 1980s. The adoption of high-yielding varieties of cannabis, modern agricultural practices, and modern hashish production techniques began in the mid-2000s and accelerated after the mid-2010s, with the result that more potent and varied cannabis derivatives are now being produced and that increased quantities of highly potent hashish are seized in Europe. This research was initiated to answer a simple research question: how, and to what extent, is the illegal cannabis industry modernizing in Morocco, now that we know that it explains the THC increase in hashish seized in Europe? To answer this question in the context of a lack of literature and quantitative data, empirical fieldwork was undertaken in cannabis fields and hashish-producing farms in Morocco in July and October 2017. A mostly qualitative approach to data collection was employed through participatory rural appraisals (discussions, interviews, direct observations). As such, this work builds predominantly upon primary research. Fieldwork showed that, subsequent to very localized, experimental beginnings in the early 2000s, the progressive and varied adoption of agricultural innovations at the cultivation and production stages has spread throughout the Rif during the 2010s. Interviews and direct observations conducted in the field indicate that the ongoing adoption of modern farming techniques has enabled the production of high-quality hashish and potent modern extracts. The still ongoing modernization and professionalization of the Moroccan cannabis industry is a testimony of the country's leading position in global hashish production. What the future holds for Moroccan cannabis growers is difficult to predict. How legalization processes manifest themselves in Moroccan and European policies, and how upcoming developments will affect the social, economic

Psychoactive constituents of cannabis and their clinical implications: a systematic review.

PubMed

Casajuana Köguel, Cristina; López-Pelayo, Hugo; Balcells-Olivero, Mª Mercedes; Colom, Joan; Gual, Antoni

2018-04-15

Objective This systematic review aims to summarize current evidence on which naturally present cannabinoids contribute to cannabis psychoactivity, considering their reported concentrations and pharmacodynamics in humans. Design Following PRISMA guidelines, papers published before March 2016 in Medline, Scopus-Elsevier, Scopus, ISI-Web of Knowledge and COCHRANE, and fulfilling established a-priori selection criteria have been included. Results In 40 original papers, three naturally present cannabinoids (∆-9-Tetrahydrocannabinol, ∆-8-Tetrahydrocannabinol and Cannabinol) and one human metabolite (11-OH-THC) had clinical relevance. Of these, the metabolite produces the greatest psychoactive effects. Cannabidiol (CBD) is not psychoactive but plays a modulating role on cannabis psychoactive effects. The proportion of 9-THC in plant material is higher (up to 40%) than in other cannabinoids (up to 9%). Pharmacodynamic reports vary due to differences in methodological aspects (doses, administration route and volunteers' previous experience with cannabis). Conclusions Findings reveal that 9-THC contributes the most to cannabis psychoactivity. Due to lower psychoactive potency and smaller proportions in plant material, other psychoactive cannabinoids have a weak influence on cannabis final effects. Current lack of standard methodology hinders homogenized research on cannabis health effects. Working on a standard cannabis unit considering 9-THC is recommended.

The toxicology of cannabis and cannabis prohibition.

PubMed

Grotenhermen, Franjo

2007-08-01

The acute side effects caused by cannabis use are mainly related to psyche and cognition, and to circulation. Euphoria, anxiety, changes in sensory perception, impairment of memory and psychomotor performance are common effects after a dose is taken that exceeds an individually variable threshold. Cannabis consumption may increase heart rate and change blood pressure, which may have serious consequences in people with heart disease. Effects of chronic use may be induction of psychosis and development of dependency to the drug. Effects on cognitive abilities seem to be reversible after abstinence, except possibly in very heavy users. Cannabis exposure in utero may have negative consequences on brain development with subtle impairment of cognitive abilities in later life. Consequences of cannabis smoking may be similar to those of tobacco smoking and should be avoided. Use by young people has more detrimental effects than use by adults. There appear to be promising therapeutic uses of cannabis for a range of indications. Use of moderate doses in a therapeutic context is usually not associated with severe side effects. Current prohibition on cannabis use may also have harmful side effects for the individual and the society, while having little influence on prevalence of use. Harm is greatest for seriously ill people who may benefit from a treatment with cannabis. This makes it difficult to justify criminal penalties against patients.

Medicinal cannabis: Principal cannabinoids concentration and their stability evaluated by a high performance liquid chromatography coupled to diode array and quadrupole time of flight mass spectrometry method.

PubMed

Citti, Cinzia; Ciccarella, Giuseppe; Braghiroli, Daniela; Parenti, Carlo; Vandelli, Maria Angela; Cannazza, Giuseppe

2016-09-05

In the last few years, there has been a boost in the use of cannabis-based extracts for medicinal purposes, although their preparation procedure has not been standardized but rather decided by the individual pharmacists. The present work describes the development of a simple and rapid high performance liquid chromatography method with UV detection (HPLC-UV) for the qualitative and quantitative determination of the principal cannabinoids (CBD-A, CBD, CBN, THC and THC-A) that could be applied to all cannabis-based medicinal extracts (CMEs) and easily performed by a pharmacist. In order to evaluate the identity and purity of the analytes, a high-resolution mass spectrometry (HPLC-ESI-QTOF) analysis was also carried out. Full method validation has been performed in terms of specificity, selectivity, linearity, recovery, dilution integrity and thermal stability. Moreover, the influence of the solvent (ethyl alcohol and olive oil) was evaluated on cannabinoids degradation rate. An alternative extraction method has then been proposed in order to preserve cannabis monoterpene component in final CMEs. Copyright © 2016 Elsevier B.V. All rights reserved.

Cannabis species and cannabinoid concentration preference among sleep-disturbed medicinal cannabis users.

PubMed

Belendiuk, Katherine A; Babson, Kimberly A; Vandrey, Ryan; Bonn-Miller, Marcel O

2015-11-01

Individuals report using cannabis for the promotion of sleep, and the effects of cannabis on sleep may vary by cannabis species. Little research has documented preferences for particular cannabis types or cannabinoid concentrations as a function of use for sleep disturbances. 163 adults purchasing medical cannabis for a physical or mental health condition at a cannabis dispensary were recruited. They provided self-report of (a) whether cannabis use was intended to help with sleep problems (e.g. insomnia, nightmares), (b) sleep quality (PSQI), (c) cannabis use (including preferred type), and (d) symptoms of DSM-5 cannabis dependence. 81 participants reported using cannabis for the management of insomnia and 14 participants reported using cannabis to reduce nightmares. Individuals using cannabis to manage nightmares preferred sativa to indica strains (Fisher's exact test (2) = 6.83, p < 0.05), and sativa users were less likely to endorse DSM-5 cannabis dependence compared with those who preferred indica strains (χ(2)(2) = 4.09, p < 0.05). Individuals with current insomnia (t(9) = 3.30, p < 0.01) and greater sleep latency (F(3,6) = 46.7, p < 0.001) were more likely to report using strains of cannabis with significantly higher concentrations of CBD. Individuals who reported at least weekly use of hypnotic medications used cannabis with lower THC concentrations compared to those who used sleep medications less frequently than weekly (t(17) = 2.40, p < 0.05). Associations between sleep characteristics and the type of cannabis used were observed in this convenience sample of individuals using cannabis for the management of sleep disturbances. Controlled prospective studies are needed to better characterize the impact that specific components of cannabis have on sleep. Copyright © 2015. Published by Elsevier Ltd.

Prescribing smoked cannabis for chronic noncancer pain: preliminary recommendations.

PubMed

Kahan, Meldon; Srivastava, Anita; Spithoff, Sheryl; Bromley, Lisa

2014-12-01

To offer preliminary guidance on prescribing smoked cannabis for chronic pain before the release of formal guidelines. We reviewed the literature on the analgesic effectiveness of smoked cannabis and the harms of medical and recreational cannabis use. We developed recommendations on indications, contraindications, precautions, and dosing of smoked cannabis, and categorized the recommendations based on levels of evidence. Evidence is mostly level II (well conducted observational studies) and III (expert opinion). Smoked cannabis might be indicated for patients with severe neuropathic pain conditions who have not responded to adequate trials of pharmaceutical cannabinoids and standard analgesics (level II evidence). Smoked cannabis is contraindicated in patients who are 25 years of age or younger (level II evidence); who have a current, past, or strong family history of psychosis (level II evidence); who have a current or past cannabis use disorder (level III evidence); who have a current substance use disorder (level III evidence); who have cardiovascular or respiratory disease (level III evidence); or who are pregnant or planning to become pregnant (level II evidence). It should be used with caution in patients who smoke tobacco (level II evidence), who are at increased risk of cardiovascular disease (level III evidence), who have anxiety or mood disorders (level II evidence), or who are taking higher doses of opioids or benzodiazepines (level III evidence). Cannabis users should be advised not to drive for at least 3 to 4 hours after smoking, for at least 6 hours after oral ingestion, and for at least 8 hours if they experience a subjective "high" (level II evidence). The maximum recommended dose is 1 inhalation 4 times per day (approximately 400 mg per day) of dried cannabis containing 9% delta-9-tetrahydrocannabinol (level III evidence). Physicians should avoid referring patients to "cannabinoid" clinics (level III evidence). Future guidelines should be based on

Implicit Associations and Explicit Expectancies toward Cannabis in Heavy Cannabis Users and Controls

PubMed Central

Beraha, Esther M.; Cousijn, Janna; Hermanides, Elisa; Goudriaan, Anna E.; Wiers, Reinout W.

2013-01-01

Cognitive biases, including implicit memory associations are thought to play an important role in the development of addictive behaviors. The aim of the present study was to investigate implicit affective memory associations in heavy cannabis users. Implicit positive-arousal, sedation, and negative associations toward cannabis were measured with three Single Category Implicit Association Tests (SC-IAT’s) and compared between 59 heavy cannabis users and 89 controls. Moreover, we investigated the relationship between these implicit affective associations and explicit expectancies, subjective craving, cannabis use, and cannabis related problems. Results show that heavy cannabis users had stronger implicit positive-arousal associations but weaker implicit negative associations toward cannabis compared to controls. Moreover, heavy cannabis users had stronger sedation but weaker negative explicit expectancies toward cannabis compared to controls. Within heavy cannabis users, more cannabis use was associated with stronger implicit negative associations whereas more cannabis use related problems was associated with stronger explicit negative expectancies, decreasing the overall difference on negative associations between cannabis users and controls. No other associations were observed between implicit associations, explicit expectancies, measures of cannabis use, cannabis use related problems, or subjective craving. These findings indicate that, in contrast to other substances of abuse like alcohol and tobacco, the relationship between implicit associations and cannabis use appears to be weak in heavy cannabis users. PMID:23801968

Comparing adult cannabis treatment-seekers enrolled in a clinical trial with national samples of cannabis users in the United States

PubMed Central

McClure, Erin A.; King, Jacqueline S.; Wahle, Aimee; Matthews, Abigail G.; Sonne, Susan C.; Lofwall, Michelle R.; McRae-Clark, Aimee L.; Ghitza, Udi E.; Martinez, Melissa; Cloud, Kasie; Virk, Harvir S.; Gray, Kevin M.

2017-01-01

Background Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally representative datasets from the US; 1) National Survey on Drug Use and Health, 2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3) Treatment Episodes Data Set – Admissions. Methods Comparisons were made between the clinical trial sample and appropriate cannabis using sub-samples from the national datasets, and propensity scores were calculated to determine the degree of similarity between samples. Results Results showed that the clinical trial sample was significantly different from all three national datasets, with the clinical trial sample having greater representation among older adults, African Americans, Hispanic/Latinos, adults with more education, non-tobacco users, and daily and almost daily cannabis users. Conclusions These results are consistent with previous studies of other substance use disorder populations and extend sample representation issues to a cannabis use disorder population. This illustrates the need to ensure representative samples within cannabis treatment clinical trials to improve the generalizability of promising findings. PMID:28511033

Comparing adult cannabis treatment-seekers enrolled in a clinical trial with national samples of cannabis users in the United States.

PubMed

McClure, Erin A; King, Jacqueline S; Wahle, Aimee; Matthews, Abigail G; Sonne, Susan C; Lofwall, Michelle R; McRae-Clark, Aimee L; Ghitza, Udi E; Martinez, Melissa; Cloud, Kasie; Virk, Harvir S; Gray, Kevin M

2017-07-01

Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally representative datasets from the US; 1) National Survey on Drug Use and Health, 2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3) Treatment: Episodes Data Set - Admissions. Comparisons were made between the clinical trial sample and appropriate cannabis using sub-samples from the national datasets, and propensity scores were calculated to determine the degree of similarity between samples. showed that the clinical trial sample was significantly different from all three national datasets, with the clinical trial sample having greater representation among older adults, African Americans, Hispanic/Latinos, adults with more education, non-tobacco users, and daily and almost daily cannabis users. These results are consistent with previous studies of other substance use disorder populations and extend sample representation issues to a cannabis use disorder population. This illustrates the need to ensure representative samples within cannabis treatment clinical trials to improve the generalizability of promising findings. Copyright © 2017 Elsevier B.V. All rights reserved.

An Australian nationwide survey on medicinal cannabis use for epilepsy: History of antiepileptic drug treatment predicts medicinal cannabis use.

PubMed

Suraev, Anastasia S; Todd, Lisa; Bowen, Michael T; Allsop, David J; McGregor, Iain S; Ireland, Carol; Lintzeris, Nicholas

2017-05-01

Epilepsy Action Australia conducted an Australian nationwide online survey seeking opinions on and experiences with the use of cannabis-based products for the treatment of epilepsy. The survey was promoted via the Epilepsy Action Australia's main website, on their Facebook page, and by word of mouth. The survey consisted of 39 questions assessing demographics, clinical factors, including diagnosis and seizure types, and experiences with and opinions towards cannabis use in epilepsy. A total of 976 responses met the inclusion criteria. Results show that 15% of adults with epilepsy and 13% of parents/guardians of children with epilepsy were currently using, or had previously used, cannabis products to treat epilepsy. Of those with a history of cannabis product use, 90% of adults and 71% of parents reported success in reducing seizure frequency after commencing cannabis products. The main reasons for medicinal cannabis use were to manage treatment-resistant epilepsy and to obtain a more favorable side-effect profile compared to standard antiepileptic drugs. The number of past antiepileptic drugs tried was a significant predictor of medicinal cannabis use in both adults and children with epilepsy. Fifty-six percent of adults with epilepsy and 62% of parents/guardians of children with epilepsy expressed willingness to participate in clinical trials of cannabinoids. This survey provides insight into the use of cannabis products for epilepsy, in particular some of the likely factors influencing use, as well as novel insights into the experiences of and attitudes towards medicinal cannabis in people with epilepsy in the Australian community. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy". Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Cannabis and social welfare assistance: a longitudinal study.

PubMed

Pedersen, Willy

2011-09-01

To investigate associations between cannabis use and subsequent receipt of social welfare assistance. The Young in Norway Longitudinal Study. A population-based Norwegian sample (n = 2606) was followed-up from adolescence to late 20s. Self-report data were merged with data from national registers. Data were extracted on the use of alcohol, tobacco and cannabis and other illegal substances. Information was also retrieved on socio-demographic and family factors, academic achievement, conduct problems and mental health. National registers provided data on social welfare assistance, educational level and crime statistics. We observed prospective bivariate associations between increasing levels of cannabis use and subsequent social welfare assistance (P < 0.0001). The associations were reduced after adjusting for a range of potentially confounding factors, but remained significant. Frequent cannabis users were at highly increased risk for subsequently receiving social welfare assistance. At 28 years, those with 50+ times cannabis use during the previous 12 months and had an odds ratio of 9.3 (95% confidence interval: 4.3-20.1) for receiving social welfare assistance in the following 2-year span. Users of cannabis also had longer periods of receiving social welfare assistance than others (P < 0.0001) and were less likely to leave the welfare assistance system (P < 0.0001). In Norway the use of cannabis is linked with subsequent receipt of social welfare assistance whether the consequences are related to use of the substance per se, or to cultural factors and the illegal status of the cannabis. Future research should attempt to understand the interactions of factors behind these associations. © 2011 The Author, Addiction © 2011 Society for the Study of Addiction.

E-Cigarettes: A Review of New Trends in Cannabis Use.

PubMed

Giroud, Christian; de Cesare, Mariangela; Berthet, Aurélie; Varlet, Vincent; Concha-Lozano, Nicolas; Favrat, Bernard

2015-08-21

The emergence of electronic cigarettes (e-cigs) has given cannabis smokers a new method of inhaling cannabinoids. E-cigs differ from traditional marijuana cigarettes in several respects. First, it is assumed that vaporizing cannabinoids at lower temperatures is safer because it produces smaller amounts of toxic substances than the hot combustion of a marijuana cigarette. Recreational cannabis users can discretely "vape" deodorized cannabis extracts with minimal annoyance to the people around them and less chance of detection. There are nevertheless several drawbacks worth mentioning: although manufacturing commercial (or homemade) cannabinoid-enriched electronic liquids (e-liquids) requires lengthy, complex processing, some are readily on the Internet despite their lack of quality control, expiry date, and conditions of preservation and, above all, any toxicological and clinical assessment. Besides these safety problems, the regulatory situation surrounding e-liquids is often unclear. More simply ground cannabis flowering heads or concentrated, oily THC extracts (such as butane honey oil or BHO) can be vaped in specially designed, pen-sized marijuana vaporizers. Analysis of a commercial e-liquid rich in cannabidiol showed that it contained a smaller dose of active ingredient than advertised; testing our laboratory-made, purified BHO, however, confirmed that it could be vaped in an e-cig to deliver a psychoactive dose of THC. The health consequences specific to vaping these cannabis preparations remain largely unknown and speculative due to the absence of comprehensive, robust scientific studies. The most significant health concerns involve the vaping of cannabinoids by children and teenagers. E-cigs could provide an alternative gateway to cannabis use for young people. Furthermore, vaping cannabinoids could lead to environmental and passive contamination.

E-Cigarettes: A Review of New Trends in Cannabis Use

PubMed Central

Giroud, Christian; de Cesare, Mariangela; Berthet, Aurélie; Varlet, Vincent; Concha-Lozano, Nicolas; Favrat, Bernard

2015-01-01

The emergence of electronic cigarettes (e-cigs) has given cannabis smokers a new method of inhaling cannabinoids. E-cigs differ from traditional marijuana cigarettes in several respects. First, it is assumed that vaporizing cannabinoids at lower temperatures is safer because it produces smaller amounts of toxic substances than the hot combustion of a marijuana cigarette. Recreational cannabis users can discretely “vape” deodorized cannabis extracts with minimal annoyance to the people around them and less chance of detection. There are nevertheless several drawbacks worth mentioning: although manufacturing commercial (or homemade) cannabinoid-enriched electronic liquids (e-liquids) requires lengthy, complex processing, some are readily on the Internet despite their lack of quality control, expiry date, and conditions of preservation and, above all, any toxicological and clinical assessment. Besides these safety problems, the regulatory situation surrounding e-liquids is often unclear. More simply ground cannabis flowering heads or concentrated, oily THC extracts (such as butane honey oil or BHO) can be vaped in specially designed, pen-sized marijuana vaporizers. Analysis of a commercial e-liquid rich in cannabidiol showed that it contained a smaller dose of active ingredient than advertised; testing our laboratory-made, purified BHO, however, confirmed that it could be vaped in an e-cig to deliver a psychoactive dose of THC. The health consequences specific to vaping these cannabis preparations remain largely unknown and speculative due to the absence of comprehensive, robust scientific studies. The most significant health concerns involve the vaping of cannabinoids by children and teenagers. E-cigs could provide an alternative gateway to cannabis use for young people. Furthermore, vaping cannabinoids could lead to environmental and passive contamination. PMID:26308021

The effect of cannabis use on memory function: an update.

PubMed

Schoeler, Tabea; Bhattacharyya, Sagnik

2013-01-01

Investigating the effects of cannabis use on memory function appears challenging. While early observational investigations aimed to elucidate the longer-term effects of cannabis use on memory function in humans, findings remained equivocal and pointed to a pattern of interacting factors impacting on the relationship between cannabis use and memory function, rather than a simple direct effect of cannabis. Only recently, a clearer picture of the chronic and acute effects of cannabis use on memory function has emerged once studies have controlled for potential confounding factors and started to investigate the acute effects of delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), the main ingredients in the extract of the cannabis plant in pharmacological challenge experiments. Relatively consistent findings have been reported regarding the acute impairments induced by a single dose of Δ9-THC on verbal and working memory. It is unclear whether they may persist beyond the intoxication state. In the long-term, these impairments seem particularly likely to manifest and may also persist following abstinence if regular and heavy use of cannabis strains high in Δ9-THC is started at an early age. Although still at an early stage, studies that employed advanced neuroimaging techniques have started to model the neural underpinnings of the effects of cannabis use and implicate a network of functional and morphological alterations that may moderate the effects of cannabis on memory function. Future experimental and epidemiological studies that take into consideration individual differences, particularly previous cannabis history and demographic characteristics, but also the precise mixture of the ingredients of the consumed cannabis are necessary to clarify the magnitude and the mechanisms by which cannabis-induced memory impairments occur and to elucidate underlying neurobiological mechanisms.

The effect of cannabis use on memory function: an update

PubMed Central

Schoeler, Tabea; Bhattacharyya, Sagnik

2013-01-01

Investigating the effects of cannabis use on memory function appears challenging. While early observational investigations aimed to elucidate the longer-term effects of cannabis use on memory function in humans, findings remained equivocal and pointed to a pattern of interacting factors impacting on the relationship between cannabis use and memory function, rather than a simple direct effect of cannabis. Only recently, a clearer picture of the chronic and acute effects of cannabis use on memory function has emerged once studies have controlled for potential confounding factors and started to investigate the acute effects of delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), the main ingredients in the extract of the cannabis plant in pharmacological challenge experiments. Relatively consistent findings have been reported regarding the acute impairments induced by a single dose of Δ9-THC on verbal and working memory. It is unclear whether they may persist beyond the intoxication state. In the long-term, these impairments seem particularly likely to manifest and may also persist following abstinence if regular and heavy use of cannabis strains high in Δ9-THC is started at an early age. Although still at an early stage, studies that employed advanced neuroimaging techniques have started to model the neural underpinnings of the effects of cannabis use and implicate a network of functional and morphological alterations that may moderate the effects of cannabis on memory function. Future experimental and epidemiological studies that take into consideration individual differences, particularly previous cannabis history and demographic characteristics, but also the precise mixture of the ingredients of the consumed cannabis are necessary to clarify the magnitude and the mechanisms by which cannabis-induced memory impairments occur and to elucidate underlying neurobiological mechanisms. PMID:24648785

Solitary cannabis use in adolescence as a correlate and predictor of cannabis problems.

PubMed

Creswell, Kasey G; Chung, Tammy; Clark, Duncan B; Martin, Christopher S

2015-11-01

Most adolescent cannabis use occurs in social settings among peers. Solitary cannabis use during adolescence may represent an informative divergence from normative behavior with important implications for understanding risk for cannabis problems. This longitudinal study examined associations of adolescent solitary cannabis use with levels of cannabis use and problems in adolescence and in young adulthood. Cannabis using-adolescents aged 12-18 were recruited from clinical programs (n=354; 43.8% female; 83.3% Caucasian) and community sources (n=93; 52.7% female; 80.6% Caucasian). Participants reported on cannabis use patterns and diagnostic symptoms at baseline and multiple follow-ups into young adulthood. Compared to social-only users, adolescent solitary cannabis users were more likely to be male and reported more frequent cannabis use and more DSM-IV cannabis use disorder (CUD) symptoms. Regression analyses showed that solitary cannabis use in adolescence predicted CUD symptom counts in young adulthood (age 25) after controlling for demographic variables and the frequency of adolescent cannabis use. However, solitary adolescent cannabis use was no longer predictive of age 25 CUD symptoms after additionally controlling for adolescent CUD symptoms. Solitary cannabis use is associated with greater cannabis use and problems during adolescence, but evidence is mixed that it predicts young adult cannabis problems. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Medical Cannabis and the Treatment of Obstructive Sleep Apnea: An American Academy of Sleep Medicine Position Statement.

PubMed

Ramar, Kannan; Rosen, Ilene M; Kirsch, Douglas B; Chervin, Ronald D; Carden, Kelly A; Aurora, R Nisha; Kristo, David A; Malhotra, Raman K; Martin, Jennifer L; Olson, Eric J; Rosen, Carol L; Rowley, James A

2018-04-15

The diagnosis and effective treatment of obstructive sleep apnea (OSA) in adults is an urgent health priority. Positive airway pressure (PAP) therapy remains the most effective treatment for OSA, although other treatment options continue to be explored. Limited evidence citing small pilot or proof of concept studies suggest that the synthetic medical cannabis extract dronabinol may improve respiratory stability and provide benefit to treat OSA. However, side effects such as somnolence related to treatment were reported in most patients, and the long-term effects on other sleep quality measures, tolerability, and safety are still unknown. Dronabinol is not approved by the United States Food and Drug Administration (FDA) for treatment of OSA, and medical cannabis and synthetic extracts other than dronabinol have not been studied in patients with OSA. The composition of cannabinoids within medical cannabis varies significantly and is not regulated. Synthetic medical cannabis may have differential effects, with variable efficacy and side effects in the treatment of OSA. Therefore, it is the position of the American Academy of Sleep Medicine (AASM) that medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA due to unreliable delivery methods and insufficient evidence of effectiveness, tolerability, and safety. OSA should be excluded from the list of chronic medical conditions for state medical cannabis programs, and patients with OSA should discuss their treatment options with a licensed medical provider at an accredited sleep facility. Further research is needed to understand the functionality of medical cannabis extracts before recommending them as a treatment for OSA. © 2018 American Academy of Sleep Medicine.

[Review: executive functioning and cannabis use].

PubMed

Almeida, Priscila Previato; Novaes, Maria Alice Fontes Pinto; Bressan, Rodrigo Affonseca; Lacerda, Acioly Luiz Tavares de

2008-03-01

Cannabis is the most used illicit drug worldwide, however only a few studies have examined cognitive deficits related to its use. Clinical manifestations associated with those deficits include a motivational syndrome, impairment in cognitive flexibility, inattention, deficits in abstract reasoning and concept formation, aspects intimately related to the executive functions, which potentially exert a central role in substance dependence. The objective was to make a review about consequences of cannabis use in executive functioning. This review was carried out on reports drawn from MedLine, SciELO, and Lilacs. In studies investigating acute use effects, higher doses of tetrahydrocannabinol are associated to impairments in performance of nonsevere users in planning and control impulse tasks. However, chronic cannabis users do not show those impairments. Although demonstration of residual effects of cannabis in the executive functioning is controversial, persistent deficits seem to be present at least in a subgroup of chronic users after 28 days of abstinence. The neuropsychological studies found did not have as a main aim the evaluation of executive functioning. A criterial selection of standardized neuropsychological tests, more appropriate study designs as well as concomitant investigations with structural and functional neuroimaging techniques may improve the understanding of eventual neurotoxicity associated with cannabis use.

Psychotic-like experiences with cannabis use predict cannabis cessation and desire to quit: a cannabis discontinuation hypothesis.

PubMed

Sami, Musa; Notley, Caitlin; Kouimtsidis, Christos; Lynskey, Michael; Bhattacharyya, Sagnik

2018-03-23

Evidence suggests that cannabis-induced psychotic-like experiences may be a marker of psychosis proneness. The effect of such experiences on cannabis use has not systematically been examined. We undertook a mixed-methods online survey of 1231 cannabis users (including 926 continued users) using the Cannabis Experiences Questionnaire. We examined the effect of psychotic-like and pleasurable experiences on cessation of cannabis and intention to quit. Socio-demographic variables, cannabis use parameters and substance misuse history were included as covariates. Free-text data explored subjective reasons for changes in use. Cessation of cannabis use was associated with greater psychotic-like experiences [p < 0.001, Exp(B) 1.262, 95% confidence interval (CI) 1.179-1.351], whilst continued cannabis users were more likely to report pleasurable experiences [p < 0.001, Exp(B) 0.717, 95% CI 0.662-0.776]. Intention to quit cannabis in continued users was associated with greater psychotic-like experiences [p < 0.003, Exp(B) 1.131, 95% CI 1.044-1.225], whilst intention to not quit was significantly associated with increased pleasurable experiences [p < 0.015, Exp(B) 0.892, 95% CI 0.814-0.978]. Whereas former users clearly ascribed cessation to negative experiences, continued users who expressed intention to quit less readily ascribed the intention to negative experiences. Elucidation of psychotic-like experiences may form the basis of a therapeutic intervention for those who wish to quit. Cessation in those with cannabis-induced psychotomimetic experiences may offset the risk for the development of a psychotic disorder, in this higher risk group.

Cannabis sativa allergy: looking through the fog.

PubMed

Decuyper, I I; Van Gasse, A L; Cop, N; Sabato, V; Faber, M A; Mertens, C; Bridts, C H; Hagendorens, M M; De Clerck, L; Rihs, H P; Ebo, D G

2017-02-01

IgE-mediated Cannabis (C. sativa, marihuana) allergy seems to be on the rise. Both active and passive exposure to cannabis allergens may trigger a C. sativa sensitization and/or allergy. The clinical presentation of a C. sativa allergy varies from mild to life-threatening reactions and often seems to depend on the route of exposure. In addition, sensitization to cannabis allergens can result in various cross-allergies, mostly for plant foods. This clinical entity, designated as the 'cannabis-fruit/vegetable syndrome', might also imply cross-reactivity with tobacco, natural latex and plant-food-derived alcoholic beverages. Hitherto, these cross-allergies are predominantly reported in Europe and appear mainly to rely upon cross-reactivity between nonspecific lipid transfer proteins or thaumatin-like proteins present in C. sativa and their homologues, ubiquitously distributed throughout plant kingdom. At present, diagnosis of cannabis-related allergies predominantly rests upon a thorough history completed with skin testing using native extracts from crushed buds and leaves. However, quantification of specific IgE antibodies and basophil activation tests can also be helpful to establish correct diagnosis. In the absence of a cure, treatment comprises absolute avoidance measures. Whether avoidance of further use will halt the extension of related cross-allergies remains uncertain. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development and Validation of a Reliable and Robust Method for the Analysis of Cannabinoids and Terpenes in Cannabis.

PubMed

Giese, Matthew W; Lewis, Mark A; Giese, Laura; Smith, Kevin M

2015-01-01

The requirements for an acceptable cannabis assay have changed dramatically over the years resulting in a large number of laboratories using a diverse array of analytical methodologies that have not been properly validated. Due to the lack of sufficiently validated methods, we conducted a single- laboratory validation study for the determination of cannabinoids and terpenes in a variety of commonly occurring cultivars. The procedure involves high- throughput homogenization to prepare sample extract, which is then profiled for cannabinoids and terpenes by HPLC-diode array detector and GC-flame ionization detector, respectively. Spike recovery studies for terpenes in the range of 0.03-1.5% were carried out with analytical standards, while recovery studies for Δ9-tetrahydrocannabinolic acid, cannabidiolic acid, Δ9-tetrahydrocannabivarinic acid, and cannabigerolic acid and their neutral counterparts in the range of 0.3-35% were carried out using cannabis extracts. In general, accuracy at all levels was within 5%, and RSDs were less than 3%. The interday and intraday repeatabilities of the procedure were evaluated with five different cultivars of varying chemotype, again resulting in acceptable RSDs. As an example of the application of this assay, it was used to illustrate the variability seen in cannabis coming from very advanced indoor cultivation operations.

Statistics on Cannabis Users Skew Perceptions of Cannabis Use

PubMed Central

Burns, Rachel M.; Caulkins, Jonathan P.; Everingham, Susan S.; Kilmer, Beau

2013-01-01

Collecting information about the prevalence of cannabis use is necessary but not sufficient for understanding the size, dynamics, and outcomes associated with cannabis markets. This paper uses two data sets describing cannabis consumption in the United States and Europe to highlight (1) differences in inferences about sub-populations based on the measure used to quantify cannabis-related activity; (2) how different measures of cannabis-related activity can be used to more accurately describe trends in cannabis usage over time; and (3) the correlation between frequency of use in the past-month and average grams consumed per use-day. Key findings: focusing on days of use instead of prevalence shows substantially greater increases in U.S. cannabis use in recent years; however, the recent increase is mostly among adults, not youth. Relatively more rapid growth in use days also occurred among the college-educated and Hispanics. Further, data from a survey conducted in seven European countries show a strong positive correlation between frequency of use and quantity consumed per day of use, suggesting consumption is even more skewed toward the minority of heavy users than is suggested by days-of-use calculations. PMID:24223560

Cannabis and tolerance: acute drug impairment as a function of cannabis use history

PubMed Central

Ramaekers, J. G.; van Wel, J. H.; Spronk, D. B.; Toennes, S. W.; Kuypers, K. P. C.; Theunissen, E. L.; Verkes, R. J.

2016-01-01

Cannabis use history as predictor of neurocognitive response to cannabis intoxication remains subject to scientific and policy debates. The present study assessed the influence of cannabis on neurocognition in cannabis users whose cannabis use history ranged from infrequent to daily use. Drug users (N = 122) received acute doses of cannabis (300 μg/kg THC), cocaine HCl (300 mg) and placebo. Cocaine served as active control for demonstrating neurocognitive test sensitivity. Executive function, impulse control, attention, psychomotor function and subjective intoxication were significantly worse after cannabis administration relative to placebo. Cocaine improved psychomotor function and attention, impaired impulse control and increased feelings of intoxication. Acute effects of cannabis and cocaine on neurocognitive performance were similar across cannabis users irrespective of their cannabis use history. Absence of tolerance implies that that frequent cannabis use and intoxication can be expected to interfere with neurocognitive performance in many daily environments such as school, work or traffic. PMID:27225696

Cannabis and tolerance: acute drug impairment as a function of cannabis use history.

PubMed

Ramaekers, J G; van Wel, J H; Spronk, D B; Toennes, S W; Kuypers, K P C; Theunissen, E L; Verkes, R J

2016-05-26

Cannabis use history as predictor of neurocognitive response to cannabis intoxication remains subject to scientific and policy debates. The present study assessed the influence of cannabis on neurocognition in cannabis users whose cannabis use history ranged from infrequent to daily use. Drug users (N = 122) received acute doses of cannabis (300 μg/kg THC), cocaine HCl (300 mg) and placebo. Cocaine served as active control for demonstrating neurocognitive test sensitivity. Executive function, impulse control, attention, psychomotor function and subjective intoxication were significantly worse after cannabis administration relative to placebo. Cocaine improved psychomotor function and attention, impaired impulse control and increased feelings of intoxication. Acute effects of cannabis and cocaine on neurocognitive performance were similar across cannabis users irrespective of their cannabis use history. Absence of tolerance implies that that frequent cannabis use and intoxication can be expected to interfere with neurocognitive performance in many daily environments such as school, work or traffic.

Cannabis cue reactivity and craving among never, infrequent and heavy cannabis users.

PubMed

Henry, Erika A; Kaye, Jesse T; Bryan, Angela D; Hutchison, Kent E; Ito, Tiffany A

2014-04-01

Substance cue reactivity is theorized as having a significant role in addiction processes, promoting compulsive patterns of drug-seeking and drug-taking behavior. However, research extending this phenomenon to cannabis has been limited. To that end, the goal of the current work was to examine the relationship between cannabis cue reactivity and craving in a sample of 353 participants varying in self-reported cannabis use. Participants completed a visual oddball task whereby neutral, exercise, and cannabis cue images were presented, and a neutral auditory oddball task while event-related brain potentials (ERPs) were recorded. Consistent with past research, greater cannabis use was associated with greater reactivity to cannabis images, as reflected in the P300 component of the ERP, but not to neutral auditory oddball cues. The latter indicates the specificity of cue reactivity differences as a function of substance-related cues and not generalized cue reactivity. Additionally, cannabis cue reactivity was significantly related to self-reported cannabis craving as well as problems associated with cannabis use. Implications for cannabis use and addiction more generally are discussed.

Cannabis Cue Reactivity and Craving Among Never, Infrequent and Heavy Cannabis Users

PubMed Central

Henry, Erika A; Kaye, Jesse T; Bryan, Angela D; Hutchison, Kent E; Ito, Tiffany A

2014-01-01

Substance cue reactivity is theorized as having a significant role in addiction processes, promoting compulsive patterns of drug-seeking and drug-taking behavior. However, research extending this phenomenon to cannabis has been limited. To that end, the goal of the current work was to examine the relationship between cannabis cue reactivity and craving in a sample of 353 participants varying in self-reported cannabis use. Participants completed a visual oddball task whereby neutral, exercise, and cannabis cue images were presented, and a neutral auditory oddball task while event-related brain potentials (ERPs) were recorded. Consistent with past research, greater cannabis use was associated with greater reactivity to cannabis images, as reflected in the P300 component of the ERP, but not to neutral auditory oddball cues. The latter indicates the specificity of cue reactivity differences as a function of substance-related cues and not generalized cue reactivity. Additionally, cannabis cue reactivity was significantly related to self-reported cannabis craving as well as problems associated with cannabis use. Implications for cannabis use and addiction more generally are discussed. PMID:24264815

Testicular toxicity in cannabis extract treated mice: association with oxidative stress and role of antioxidant enzyme systems.

PubMed

Mandal, Tapas K; Das, Nildari S

2010-02-01

Intraperitoneal injection of cannabis extract at low doses (total doses ranging from 40 mg to 60 mg per mouse) induced adverse effect on testes and oxidative stress. At low doses, there was a significant increase in lipid peroxidation and decrease in testicular lipid content, but the effects were significantly less at higher doses and at the withdrawal of cannabis treatment (recovery dose). There was a marked decrease in antioxidant enzyme profiles (superoxide dismutase, catalase and glutathione peroxidase) and glutathione content at low doses, but these effects were higher at higher dose and at withdrawal of the treatment (recovery effect). Histology revealed significant shrinkage of tubular diameter and detrimental changes in seminiferous epithelium of testis with resulting lowered serum testosterone and pituitary gonadotropins (follicular stimulating [FSH] and luteinizing hormones [LH]) levels at low doses. But at higher doses and particularly at withdrawal of the treatment, regression of various germ cell layers of testes through the revival of testosterone hormone and pituitary gonadotropins (FSH and LH) were observed, indicating that recovery effects on testes became operative possibly through the corrective measure of endogenous testicular antioxidant enzymes profiles and pituitary gonadotropins hormones feedback mechanisms.

Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS).

PubMed

Ware, Mark A; Wang, Tongtong; Shapiro, Stan; Collet, Jean-Paul

2015-12-01

Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic non-cancer pain. The safety of cannabis use for medical purposes has not been systematically evaluated. We conducted a prospective cohort study to describe safety issues among individuals with chronic non-cancer pain. A standardized herbal cannabis product (12.5% tetrahydrocannabinol) was dispensed to eligible individuals for a 1-year period; controls were individuals with chronic pain from the same clinics who were not cannabis users. The primary outcome consisted of serious adverse events and non-serious adverse events. Secondary safety outcomes included pulmonary and neurocognitive function and standard hematology, biochemistry, renal, liver, and endocrine function. Secondary efficacy parameters included pain and other symptoms, mood, and quality of life. Two hundred and fifteen individuals with chronic pain were recruited to the cannabis group (141 current users and 58 ex-users) and 216 controls (chronic pain but no current cannabis use) from 7 clinics across Canada. The median daily cannabis dose was 2.5 g/d. There was no difference in risk of serious adverse events (adjusted incidence rate ratio = 1.08, 95% confidence interval = .57-2.04) between groups. Medical cannabis users were at increased risk of non-serious adverse events (adjusted incidence rate ratio = 1.73, 95% confidence interval = 1.41-2.13); most were mild to moderate. There were no differences in secondary safety assessments. Quality-controlled herbal cannabis, when used by patients with experience of cannabis use as part of a monitored treatment program over 1 year, appears to have a reasonable safety profile. Longer-term monitoring for functional outcomes is needed. The study was registered with www.controlled-trials.com (ISRCTN19449752). This study evaluated the safety of cannabis use by patients with chronic pain over 1 year. The study found that there was a higher

INVESTIGATION OF SEX-DEPENDENT EFFECTS OF CANNABIS IN DAILY CANNABIS SMOKERS

PubMed Central

Cooper, Ziva D.; Haney, Margaret

2014-01-01

Background Women exhibit an accelerated progression from first cannabis use to cannabis use disorder (CUD) and show pronounced negative clinical issues related to CUD relative to men. Whether sex-dependent differences in cannabis’ direct effects contribute to the heightened risk in women is unknown. This analysis directly compared cannabis’ abuse-related subjective effects in men and women matched for current cannabis use. Methods Data from four double-blind, within-subject studies measuring the effects of active cannabis (3.27–5.50% THC, depending on study) relative to inactive cannabis (0.00% THC) were combined for this analysis. Data from equal numbers of men and women from each study matched for current cannabis use were pooled (total n = 35 men; 35 women); cannabis’ effects were analyzed according to cannabis condition (active versus inactive) and sex. Results Active cannabis produced more robust subjective effects associated with abuse liability (‘Good,’ ‘Liking,’ ‘Take Again’) and intoxication (‘High,’ ‘Stimulated’) relative to inactive cannabis (p • 0.0001). Women reported higher ratings of abuse-related effects [‘Take Again’ and ‘Good’ (p • 0.05)] relative to men under active cannabis conditions but did not differ in ratings of intoxication. Active cannabis increased heart rate (p • 0.0001) equally for both sexes. Conclusions The results from this study suggest that when matched for cannabis use, women are more sensitive to the subjective effects related to cannabis’ abuse liability relative to men, which may contribute to the enhanced vulnerability to developing CUD. Thus, sex is an important variable to consider when assessing the development of CUD. PMID:24440051

[Medicinal cannabis].

PubMed

Van der Meersch, H; Verschuere, A P; Bottriaux, F

2006-01-01

Pharmaceutical grade cannabis is available to Dutch patients from public pharmacies in the Netherlands. The first part of this paper reviews the pharmaceutical and pharmacological properties of medicinal cannabis. Detailed information about its composition and quality, potential applications, methods of administration, adverse reactions, drug interactions and safety during pregnancy or breastfeeding are given. The second part deals with the legal aspects of dispensing medicinal cannabis through pharmacies in view of the Belgian and Dutch legislation. The last part discusses the present Belgian regulation about the possession of cannabis.

Big data on a big new market: Insights from Washington State's legal cannabis market.

PubMed

Caulkins, Jonathan P; Bao, Yilun; Davenport, Steve; Fahli, Imane; Guo, Yutian; Kinnard, Krista; Najewicz, Mary; Renaud, Lauren; Kilmer, Beau

2018-07-01

Voters in eight U.S. states have passed initiatives to legalize large-scale commercial production of cannabis for non-medical use. All plan or require some form of "seed-to-sale" tracking systems, which provide a view of cannabis market activity at a heretofore unimagined level of detail. Legal markets also create a range of new matters for policy makers to address. Publicly available data were obtained on approximately 45 million individually priced items purchased in the 35 million retail transactions that took place during the first two and a half years of Washington State's legal cannabis market. Records include product type (flower, extract, lotion, liquid edible, etc.), product name, price, and potency with respect to multiple cannabinoids, notably THC and CBD. Items sold can be traced back up the supply chain through the store to the processor and producer, to the level of identifying the specific production batch and mother plant, the firm that tested the product, and test results. Data visualization methods are employed to describe spatial-temporal patterns of multiple correlated attributes (e.g., price and potency) broken down by product. Text-analytic methods are used to subdivide the broad category of "extracts for inhalation" into more homogeneous sub-categories. To understand the competitiveness of the legal cannabis market in Washington we calculate the Herfindahl-Hirschman index (HHI) for processors and retailers. Cannabis prices fell steadily and proportionally at the processor and retailer levels. Retail and wholesale price maintained a roughly 3:1 ratio for multiple product types after some initial fluctuations. Although a wide range of edibles are sold, they account for a modest share of consumer spending; extracts for inhalation are a larger and heterogeneous market segment. The HHI indicates the cannabis market is highly competitive at the processor level, but less so for retail markets at the county level. Washington's state-legal cannabis

Cannabis cultivation: Methodological issues for obtaining medical-grade product.

PubMed

Chandra, Suman; Lata, Hemant; ElSohly, Mahmoud A; Walker, Larry A; Potter, David

2017-05-01

As studies continue to reveal favorable findings for the use of cannabidiol in the management of childhood epilepsy syndromes and other disorders, best practices for the large-scale production of Cannabis are needed for timely product development and research purposes. The processes of two institutions with extensive experience in producing large-scale cannabidiol chemotype Cannabis crops-GW Pharmaceuticals and the University of Mississippi-are described, including breeding, indoor and outdoor growing, harvesting, and extraction methods. Such practices have yielded desirable outcomes in Cannabis breeding and production: GW Pharmaceuticals has a collection of chemotypes dominant in any one of eight cannabinoids, two of which-cannabidiol and cannabidivarin-are supporting epilepsy clinical trial research, whereas in addition to a germplasm bank of high-THC, high-CBD, and intermediate type cannabis varieties, the team at University of Mississippi has established an in vitro propagation protocol for cannabis with no detectable variations in morphologic, physiologic, biochemical, and genetic profiles as compared to the mother plants. Improvements in phytocannabinoid yields and growing efficiency are expected as research continues at these institutions. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy". Copyright © 2016. Published by Elsevier Inc.

Quantitative Criteria to Screen for Cannabis Use Disorder.

PubMed

Casajuana, Cristina; López-Pelayo, Hugo; Miquel, Laia; Balcells-Oliveró, María Mercedes; Colom, Joan; Gual, Antoni

2018-06-27

The Standard Joint Unit (1 SJU = 7 mg of 9-Tetrahydrocannabinol) simplifies the exploration of risky patterns of cannabis use. This study proposes a preliminary quantitative cutoff criterion to screen for cannabis use disorder (CUD). Socio-demographical data and information on cannabis quantities, frequency of use, and risk for CUD (measured with the Cannabis Abuse Screening Test (CAST) of cannabis users recruited in Barcelona (from February 2015 to June 2016) were collected. CAST scores were categorized into low, moderate, and high risk for CUD, based on the SJU consumed and frequency. Receiver operating characteristic (ROC) analysis related daily SJU with CUD. Participants (n = 473) were on average 29 years old (SD = 10), men (77.1%), and single (74.6%). With an average of 4 joints per smoking day, 82.5% consumed cannabis almost every day. Risk for CUD (9.40% low, 23.72% moderate, 66.88% high) increased significantly with more frequency and quantities consumed. The ROC analyses suggest 1.2 SJU per day as a cutoff criterion to screen for at least moderate risk for CUD (sensitivity 69.4%, specificity 63.6%). Frequency and quantity should be considered when exploring cannabis risks. A 1 SJU per day is proposed as a preliminary quantitative-based criterion to screen users with at least a moderate risk for CUD. © 2018 S. Karger AG, Basel.

The chronic effects of cannabis on memory in humans: a review.

PubMed

Solowij, Nadia; Battisti, Robert

2008-01-01

Memory problems are frequently associated with cannabis use, in both the short- and long-term. To date, reviews on the long-term cognitive sequelae of cannabis use have examined a broad range of cognitive functions, with none specifically focused on memory. Consequently, this review sought to examine the literature specific to memory function in cannabis users in the nontoxicated state with the aim of identifying the existence and nature of memory impairment in cannabis users and appraising potentially related mediators or moderators. Literature searches were conducted to extract well-controlled studies that investigated memory function in cannabis users outside of the acute intoxication period, with a focus on reviewing studies published within the past 10 years. Most recent studies have examined working memory and verbal episodic memory and cumulatively, the evidence suggests impaired encoding, storage, manipulation and retrieval mechanisms in long-term or heavy cannabis users. These impairments are not dissimilar to those associated with acute intoxication and have been related to the duration, frequency, dose and age of onset of cannabis use. We consider the impact of not only specific parameters of cannabis use in the manifestation of memory dysfunction, but also such factors as age, neurodevelopmental stage, IQ, gender, various vulnerabilities and other substance-use interactions, in the context of neural efficiency and compensatory mechanisms. The precise nature of memory deficits in cannabis users, their neural substrates and manifestation requires much further exploration through a variety of behavioural, functional brain imaging, prospective and genetic studies.

Medical Cannabis and the Treatment of Obstructive Sleep Apnea: An American Academy of Sleep Medicine Position Statement

PubMed Central

Ramar, Kannan; Rosen, Ilene M.; Kirsch, Douglas B.; Chervin, Ronald D.; Carden, Kelly A.; Aurora, R. Nisha; Kristo, David A.; Malhotra, Raman K.; Martin, Jennifer L.; Olson, Eric J.; Rosen, Carol L.; Rowley, James A.

2018-01-01

The diagnosis and effective treatment of obstructive sleep apnea (OSA) in adults is an urgent health priority. Positive airway pressure (PAP) therapy remains the most effective treatment for OSA, although other treatment options continue to be explored. Limited evidence citing small pilot or proof of concept studies suggest that the synthetic medical cannabis extract dronabinol may improve respiratory stability and provide benefit to treat OSA. However, side effects such as somnolence related to treatment were reported in most patients, and the long-term effects on other sleep quality measures, tolerability, and safety are still unknown. Dronabinol is not approved by the United States Food and Drug Administration (FDA) for treatment of OSA, and medical cannabis and synthetic extracts other than dronabinol have not been studied in patients with OSA. The composition of cannabinoids within medical cannabis varies significantly and is not regulated. Synthetic medical cannabis may have differential effects, with variable efficacy and side effects in the treatment of OSA. Therefore, it is the position of the American Academy of Sleep Medicine (AASM) that medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA due to unreliable delivery methods and insufficient evidence of effectiveness, tolerability, and safety. OSA should be excluded from the list of chronic medical conditions for state medical cannabis programs, and patients with OSA should discuss their treatment options with a licensed medical provider at an accredited sleep facility. Further research is needed to understand the functionality of medical cannabis extracts before recommending them as a treatment for OSA. Citation: Ramar K, Rosen IM, Kirsch DB, Chervin RD, Carden KA, Aurora RN, Kristo DA, Malhotra RK, Martin JL, Olson EJ, Rosen CL, Rowley JA; American Academy of Sleep Medicine Board of Directors. Medical cannabis and the treatment of obstructive sleep apnea: an

Do recreational cannabis users, unlicensed and licensed medical cannabis users form distinct groups?

PubMed

Sznitman, Sharon R

2017-04-01

This study aims to gain a more nuanced perspective on the differences between recreationally and medically motivated cannabis use by distinguishing between people who use cannabis for recreational purposes, unlicensed and licensed medical users. Data collection was conducted online from a convenience sample of 1479 Israeli cannabis users. Multinomial regression analysis compared unlicensed medical users (38%) with recreational (42%) and licensed medical (5.6%) users in terms of sociodemographics, mode, frequency and problematic cannabis use. There were more variables distinguishing unlicensed from licensed users than there were distinguishing features between unlicensed and recreational users. Recreational users were more likely to be male, less likely to eat cannabis, to use cannabis frequently and to use alone and before midday than unlicensed users. Licensed users were older than unlicensed users, they reported less hours feeling stoned, less cannabis use problems and they were more likely to report cannabis use patterns analogous of medication administration for chronic problems (frequent use, vaping, use alone and use before midday). This study suggests that a sizable proportion of cannabis users in Israel self-prescribe cannabis and that licensed medical cannabis users differ from unlicensed users. This is, in turn, suggestive of a rigorous medicalized cannabis program that does not function as a backdoor for legal access to recreational use. However, due to methodological limitations this conclusion is only suggestive. The most meaningful differences across recreational, unlicensed and licensed users were mode and patterns of use rather than cannabis use problems. Current screening tools for cannabis use problems may, however, not be well suited to assess such problems in medically motivated users. Indeed, when screening for problematic cannabis use there is a need for a more careful consideration of whether or not cannabis use is medically motivated

[Cannabis: Use and dependence].

PubMed

Dervaux, Alain; Laqueille, Xavier

2012-12-01

The main characteristics of cannabis dependence are craving, persistent desire or unsuccessful efforts to cut down or control cannabis use and important social, occupational, or recreational activities given up or reduced because of cannabis use. Withdrawal symptoms include insomnia, irritability, anger, restlessness, depression, mood swings and cravings. Regular cannabis use induces cognitive impairment, especially of attention, episodic memory and working memory. Alcohol and other substances abuse or dependence are frequently found in patients with cannabis dependence. Psychiatric comorbidities are frequent in patients with cannabis dependence, in particular anxiety disorders, mood disorders, and personality disorders. The treatment of cannabis dependence includes behavioral psychotherapy, especially motivational interviewing and cognitive-behavioral therapy, alongside treatment of co-occurring mental health and substance use conditions. There are currently no available pharmacological treatment interventions for cannabis dependence. The treatment of cannabis dependence and withdrawal remains nonspecific. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

On the move: Exploring the impact of residential mobility on cannabis use.

PubMed

Morris, Tim; Manley, David; Northstone, Kate; Sabel, Clive E

2016-11-01

A large literature exists suggesting that residential mobility leads to increased participation in risky health behaviours such as cannabis use amongst youth. However, much of this work fails to account for the impact that underlying differences between mobile and non-mobile youth have on this relationship. In this study we utilise multilevel models with longitudinal data to simultaneously estimate between-child and within-child effects in the relationship between residential mobility and cannabis use, allowing us to determine the extent to which cannabis use in adolescence is driven by residential mobility and unobserved confounding. Data come from a UK cohort, The Avon Longitudinal Study of Parents and Children. Consistent with previous research we find a positive association between cumulative residential mobility and cannabis use when using multilevel extensions of conventional logistic regression models (log odds: 0.94, standard error: 0.42), indicating that children who move houses are more likely to use cannabis than those who remain residentially stable. However, decomposing this relationship into within- and between-child components reveals that the conventional model is underspecified and misleading; we find that differences in cannabis use between mobile and non-mobile children are due to underlying differences between these groups (between-child log odds: 3.56, standard error: 1.22), not by a change in status of residential mobility (within-child log odds: 1.33, standard error: 1.02). Our findings suggest that residential mobility in the teenage years does not place children at an increased risk of cannabis use throughout these years. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Validation of the Cannabis Expectancy Questionnaire (CEQ) in adult cannabis users in treatment.

PubMed

Connor, Jason P; Gullo, Matthew J; Feeney, Gerald F X; Young, Ross McD

2011-06-01

Outcome expectancies are a key cognitive construct in the etiology, assessment and treatment of Substance Use Disorders. There is a research and clinical need for a cannabis expectancy measure validated in a clinical sample of cannabis users. The Cannabis Expectancy Questionnaire (CEQ) was subjected to exploratory (n=501, mean age 27.45, 78% male) and confirmatory (n=505, mean age 27.69, 78% male) factor analysis in two separate samples of cannabis users attending an outpatient cannabis treatment program. Weekly cannabis consumption was clinically assessed and patients completed the Severity of Dependence Scale-Cannabis (SDS-C) and the General Health Questionnaire (GHQ-28). Two factors representing Negative Cannabis Expectancies and Positive Cannabis Expectancies were identified. These provided a robust statistical and conceptual fit for the data. Internal reliabilities were high. Negative expectancies were associated with greater dependence severity (as measured by the SDS) and positive expectancies with higher consumption. The interaction of positive and negative expectancies was consistently significantly associated with self-reported functioning across all four GHQ-28 scales (Somatic Concerns, Anxiety, Social Dysfunction and Depression). Specifically, within the context of high positive cannabis expectancy, higher negative expectancy was predictive of more impaired functioning. By contrast, within the context of low positive cannabis expectancy, higher negative expectancy was predictive of better functioning. The CEQ is the first cannabis expectancy measure to be validated in a sample of cannabis users in treatment. Negative and positive cannabis expectancy domains were uniquely associated with consumption, dependence severity and self-reported mental health functioning. Crown Copyright © 2010. Published by Elsevier Ireland Ltd. All rights reserved.

Medical Cannabis in Arizona: Patient Characteristics, Perceptions, and Impressions of Medical Cannabis Legalization.

PubMed

Troutt, William D; DiDonato, Matthew D

2015-01-01

Many advances have been made toward understanding the benefits of medical cannabis. However, less is known about medical cannabis patients themselves. Prior research has uncovered many important patient characteristics, but most of that work has been conducted with participants in California, who may not represent medical cannabis patients throughout the United States. Furthermore, it is unknown if medical cannabis legalization, which typically imposes strict regulations on cannabis cultivation and sale, impacts patients' experiences acquiring and using cannabis. The goal of this study was to address these limitations by (1) examining the characteristics, perceptions, and behaviors of medical cannabis patients in Arizona; and (2) questioning participants with a history of cannabis use regarding their experiences with cannabis before and after legalization. Patients in Arizona share many characteristics with those in California, but also key differences, such as average age and degree of cannabis consumption. Participants also had positive perceptions of the effect of medical cannabis legalization, reporting that feelings of safety and awareness were higher after legalization compared to before. The results are discussed in relation to evidence from patients in other states and in terms of their potential policy implications.

Practical considerations in medical cannabis administration and dosing.

PubMed

MacCallum, Caroline A; Russo, Ethan B

2018-03-01

Cannabis has been employed medicinally throughout history, but its recent legal prohibition, biochemical complexity and variability, quality control issues, previous dearth of appropriately powered randomised controlled trials, and lack of pertinent education have conspired to leave clinicians in the dark as to how to advise patients pursuing such treatment. With the advent of pharmaceutical cannabis-based medicines (Sativex/nabiximols and Epidiolex), and liberalisation of access in certain nations, this ignorance of cannabis pharmacology and therapeutics has become untenable. In this article, the authors endeavour to present concise data on cannabis pharmacology related to tetrahydrocannabinol (THC), cannabidiol (CBD) et al., methods of administration (smoking, vaporisation, oral), and dosing recommendations. Adverse events of cannabis medicine pertain primarily to THC, whose total daily dose-equivalent should generally be limited to 30mg/day or less, preferably in conjunction with CBD, to avoid psychoactive sequelae and development of tolerance. CBD, in contrast to THC, is less potent, and may require much higher doses for its adjunctive benefits on pain, inflammation, and attenuation of THC-associated anxiety and tachycardia. Dose initiation should commence at modest levels, and titration of any cannabis preparation should be undertaken slowly over a period of as much as two weeks. Suggestions are offered on cannabis-drug interactions, patient monitoring, and standards of care, while special cases for cannabis therapeutics are addressed: epilepsy, cancer palliation and primary treatment, chronic pain, use in the elderly, Parkinson disease, paediatrics, with concomitant opioids, and in relation to driving and hazardous activities. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Cannabis for Pain and Headaches: Primer.

PubMed

Kim, Philip S; Fishman, Michael A

2017-04-01

Marijuana has been used both medicinally and recreationally since ancient times and interest in its compounds for pain relief has increased in recent years. The identification of our own intrinsic, endocannabinoid system has laid the foundation for further research. Synthetic cannabinoids are being developed and synthesized from the marijuana plant such as dronabinol and nabilone. The US Food and Drug Administration approved the use of dronabinol and nabilone for chemotherapy-associated nausea and vomiting and HIV (Human Immunodeficiency Virus) wasting. Nabiximols is a cannabis extract that is approved for the treatment of spasticity and intractable pain in Canada and the UK. Further clinical trials are studying the effect of marijuana extracts for seizure disorders. Phytocannabinoids have been identified as key compounds involved in analgesia and anti-inflammatory effects. Other compounds found in cannabis such as flavonoids and terpenes are also being investigated as to their individual or synergistic effects. This article will review relevant literature regarding medical use of marijuana and cannabinoid pharmaceuticals with an emphasis on pain and headaches.

Self-reported cannabis use characteristics, patterns and helpfulness among medical cannabis users.

PubMed

Bonn-Miller, Marcel O; Boden, Matthew Tyler; Bucossi, Meggan M; Babson, Kimberly A

2014-01-01

Little research has investigated the demographic and symptom profile of medical cannabis users in states in the USA that have legalized cannabis use. In the present cross-sectional study, we investigated the demographic profile of 217 adults currently receiving medical cannabis, as well as differences in problematic use and perceived helpfulness in terms of (i) symptoms of psychological disorders and pain, and (ii) motives for use. Findings indicated that medical cannabis users (i) use and perceive cannabis to be beneficial for multiple conditions, some for which cannabis is not specifically prescribed or allowed at the state level; and (ii) report similar rates of disordered use as compared with population estimates among regular users. Furthermore, problematic cannabis use was predicted by several symptoms of psychological disorders (e.g. depression) and a variety of use motives (e.g. coping), while cannabis was reported as particularly helpful among those with several psychological symptoms (e.g. traumatic intrusions), as well as those reporting use for social anxiety reasons. Results are discussed in terms of future directions for research given the current debates regarding legalization of cannabis for medical purposes and, more generally, the lack of empirical data to inform such debates.

Cannabis-associated arterial disease.

PubMed

Desbois, Anne Claire; Cacoub, Patrice

2013-10-01

The aim of this study was to describe the different arterial complications reported in cannabis smokers. This study was a literature review. Cannabis use was found to be associated with stroke, myocardial infarction, and lower limb arteritis. Arterial disease involved especially young men. There was a very strong temporal link between arterial complications and cannabis use for stroke and myocardial infarction episodes. Patient outcome was closely correlated with cannabis withdrawal and relapses associated with cannabis rechallenge. Cannabis use was associated with particular characteristics of arterial disease. The increased risk of myocardial infarction onset occurred within 1 hour of smoking marijuana compared with periods of non-use. Strokes occurred mainly in the posterior cerebral circulation. Compared with cohorts of thromboangiitis obliterans patients, those with cannabis-associated limb arteritis were younger, more often male, and had more frequent unilateral involvement of the lower limbs at clinical presentation. Cannabis use is associated with arterial disease such as stroke, myocardial infarction, and limbs arteritis. It appears essential to investigate cannabis use in young patients presenting with such arterial manifestations, as outcome is closely correlated with cannabis withdrawal. Copyright © 2013 Elsevier Inc. All rights reserved.

Lower-Risk Cannabis Use Guidelines: A Comprehensive Update of Evidence and Recommendations.

PubMed

Fischer, Benedikt; Russell, Cayley; Sabioni, Pamela; van den Brink, Wim; Le Foll, Bernard; Hall, Wayne; Rehm, Jürgen; Room, Robin

2017-08-01

Cannabis use is common in North America, especially among young people, and is associated with a risk of various acute and chronic adverse health outcomes. Cannabis control regimes are evolving, for example toward a national legalization policy in Canada, with the aim to improve public health, and thus require evidence-based interventions. As cannabis-related health outcomes may be influenced by behaviors that are modifiable by the user, evidence-based Lower-Risk Cannabis Use Guidelines (LRCUG)-akin to similar guidelines in other health fields-offer a valuable, targeted prevention tool to improve public health outcomes. To systematically review, update, and quality-grade evidence on behavioral factors determining adverse health outcomes from cannabis that may be modifiable by the user, and translate this evidence into revised LRCUG as a public health intervention tool based on an expert consensus process. We used pertinent medical search terms and structured search strategies, to search MEDLINE, EMBASE, PsycINFO, Cochrane Library databases, and reference lists primarily for systematic reviews and meta-analyses, and additional evidence on modifiable risk factors for adverse health outcomes from cannabis use. We included studies if they focused on potentially modifiable behavior-based factors for risks or harms for health from cannabis use, and excluded studies if cannabis use was assessed for therapeutic purposes. We screened the titles and abstracts of all studies identified by the search strategy and assessed the full texts of all potentially eligible studies for inclusion; 2 of the authors independently extracted the data of all studies included in this review. We created Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow-charts for each of the topical searches. Subsequently, we summarized the evidence by behavioral factor topic, quality-graded it by following standard (Grading of Recommendations Assessment, Development, and Evaluation; GRADE

The Cannabis Information Helpline: Assessing Interest in the Medicinal Use of Cannabis in Australia.

PubMed

Gates, Peter J; Albertella, Lucy

2017-10-15

The majority of Australians support a change in legislation to allow the use of cannabis for medical purposes. Despite strong public support, very little is known about the patterns of medicinal cannabis use among Australians. This study aims to gain a better understanding of Australian medicinal cannabis users and their patterns of use. The nature of calls to the Cannabis Information and Helpline (N = 15701), a free national service for Australians with concerns regarding cannabis use, were investigated to determine the number of calls made by those who inquired about the medicinal use of cannabis (N = 275) and the implied reasons for use among those who identify using cannabis in this way. The majority of medicinal cannabis inquirers mentioned cannabis to alleviate pain. Further, compared to other callers, medicinal cannabis inquirers were more likely to be male, unemployed, older, and have recently started using cannabis. These findings highlight the need for future research to better understand the issues faced by Australians regarding the use of cannabis for medicinal purposes and how they may be meaningfully addressed. Particular focus should be placed toward older, unemployed males.

[Cannabis: A Cognitive Illusion].

PubMed

Galván, Gonzalo; Guerrero-Martelo, Manuel; Vásquez De la Hoz, Francisco

The vision of cannabis as a soft drug is due to the low risk perception that young and old people have of the drug. This perception is based on erroneous beliefs that people have about the drug. To compare the beliefs of cannabis use and consequences among adolescents with a lifetime prevalence of cannabis use and those without a lifetime prevalence of cannabis use. Quantitative, descriptive and cross-sectional study with a probability sample of 156 high school students who completed an ad-hoc questionnaire that included sociodemographic data and 22 questions about the beliefs that young people had about cannabis use and its consequences. The lifetime prevalence of cannabis use was 13.5%. The prevalence group consisted mostly of males. Statistically significant differences between different groups and different beliefs were found. The group with no lifetime prevalence of cannabis use perceived higher risk as regards the damage that cannabis can cause to memory, other cognitive functions, neurons, mental health, and general health. The group with a lifetime prevalence of cannabis use perceived a lower risk as regards the use of cannabis, and think that intelligent people smoke cannabis, and that cannabis has positive effects on the brain, increasing creativity. and is used to cure mental diseases. Those who used cannabis once in their life perceive the use of the substance as less harmful or less potential danger to health compared to those who never consumed. In fact those who consumed at some time even have beliefs that suggest positive effects in those people that consume it. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Metabolic analysis of elicited cell suspension cultures of Cannabis sativa L. by (1)H-NMR spectroscopy.

PubMed

Pec, Jaroslav; Flores-Sanchez, Isvett Josefina; Choi, Young Hae; Verpoorte, Robert

2010-07-01

Cannabis sativa L. plants produce a diverse array of secondary metabolites. Cannabis cell cultures were treated with jasmonic acid (JA) and pectin as elicitors to evaluate their effect on metabolism from two cell lines using NMR spectroscopy and multivariate data analysis. According to principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA), the chloroform extract of the pectin-treated cultures were more different than control and JA-treated cultures; but in the methanol/water extract the metabolome of the JA-treated cells showed clear differences with control and pectin-treated cultures. Tyrosol, an antioxidant metabolite, was detected in cannabis cell cultures. The tyrosol content increased after eliciting with JA.

Cannabis Use in Psychiatrie Patients.

PubMed

Chaudhury, S; Sudarsanan, S; Salujha, S K; Srivastava, K

2005-02-01

Cannabis abuse has been associated with psychiatric disorders. The pattern of cannabis use and incidence of cannabis dependence and cannabis psychosis among 471 consecutive patients admitted to a tertiary care psychiatric center was investigated. Cannabis use was reported by 67 (14.23%) patients of whom 42 (8.92%) were occasional users, 18 (3.82%) were classified as frequent users while 7 (1.49%) fulfilled criteria for cannabis dependence. 3 (0.64%) patients showed symptoms which were characteristic of cannabis psychosis. Among the 67 cannabis users, 56 (83.58%) had their first exposure to cannabis before entering service at 13-19 years of age. The remaining 14 (16.09%) began consuming cannabis 1-5 years after joining service. The reasons given for using cannabis were curiosity about its effects 32 (47.76%), peer pressure 17 (25.37%) or traditional use during festivals 18 (26.87%).

[Systematic review of safeness and therapeutic efficacy of cannabis in patients with multiple sclerosis, neuropathic pain, and in oncological patients treated with chemotherapy].

PubMed

Amato, Laura; Minozzi, Silvia; Mitrova, Zuzana; Parmelli, Elena; Saulle, Rosella; Cruciani, Fabio; Vecchi, Simona; Davoli, Marina

2017-01-01

medical cannabis refers to the use of cannabis or cannabinoids as medical therapy to treat disease or alleviate symptoms. In the United States, 23 states and Washington DC (May 2015) have introduced laws to permit the medical use of cannabis. Within the European Union, medicinal cannabis laws and praxis vary wildly between Countries. to provide evidence for benefits and harms of cannabis (including extracts and tinctures) treatment for adults in the following indications: control of spasticity and pain in patients with multiple sclerosis; control of pain in patients with chronic neuropathic pain; control of nausea and vomiting in adults with cancer receiving chemotherapy. we searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE from inception to September 2016. We also searched for on-going studies via ClinicalTrials.gov and the World Health Organization and International Clinical Trials Registry Platform (ICTRP) search portal. All searches included also non-English language literature. All relevant randomized controlled trials (RCTs) evaluating the safety and efficacy of cannabis (including extracts and tinctures) compared with placebo or other pharmacological agents were included. Three authors independently evaluated the titles and abstracts of studies identified in the literature searches for their eligibility. For studies considered eligible, we retrieved full texts. Three investigators independently extracted data. For the assessment of the quality of evidence, we used the standard methodological procedures recommended by Cochrane and GRADE working Group. 41 trials (4,550 participants) were included; 15 studies considered efficacy and safety of cannabis for patients with multiple sclerosis, 12 for patients with chronic pain, and 14 for patients with cancer receiving chemotherapy. The included studies were published between 1975 and 2015, and the majority of them were conducted in Europe. We judged almost 50% of these studies to be at

Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers.

PubMed

Haney, Margaret; Ramesh, Divya; Glass, Andrew; Pavlicova, Martina; Bedi, Gillinder; Cooper, Ziva D

2015-10-01

Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n=18 M and 5 F) or placebo (0 mg; n=26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4-6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects ('good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1-51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of 'good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder.

Detection of Δ9-tetrahydrocannabinol in exhaled breath collected from cannabis users.

PubMed

Beck, Olof; Sandqvist, Sören; Dubbelboer, Ilse; Franck, Johan

2011-10-01

Exhaled breath has recently been proposed as a new possible matrix for drugs of abuse testing. A key drug is cannabis, and the present study was aimed at investigating the possibility of detecting tetrahydrocannabinol and tetrahydrocannabinol carboxylic acid in exhaled breath after cannabis smoking. Exhaled breath was sampled from 10 regular cannabis users and 8 controls by directing the exhaled breath by suction through an Empore C(18) disk. The disk was extracted with hexane/ethyl acetate, and the resulting extract was evaporated to dryness and redissolved in 100 μL hexane/ethyl acetate. A 3-μL aliquot was injected onto the LC-MS-MS system and analyzed using positive electrospray ionization and selected reaction monitoring. In samples collected 1-12 h after cannabis smoking, tetrahydrocannabinol was detected in all 10 subjects. The rate of excretion was between 9.0 and 77.3 pg/min. Identification of tetrahydrocannabinol was based on correct retention time relative to tetrahydrocannabinol-d(3) and correct product ion ratio. In three samples, peaks were observed for tetrahydrocannabinol carboxylic acid, but these did not fulfill identification criteria. Neither tetrahydrocannabinol or tetrahydrocannabinol carboxylic acid was detected in the controls. These results confirm older reports that tetrahydrocannabinol is present in exhaled breath following cannabis smoking and extend the detection time from minutes to hours. The results further support the idea that exhaled breath is a promising matrix for drugs-of-abuse testing.

Prevalence and correlates of "Vaping" as a route of cannabis administration in medical cannabis patients.

PubMed

Cranford, James A; Bohnert, Kipling M; Perron, Brian E; Bourque, Carrie; Ilgen, Mark

2016-12-01

To examine the prevalence and correlates of vaporization (i.e., "vaping") as a route of cannabis administration in a sample of medical cannabis patients. Adults ages 21 and older (N=1485M age=45.1) who were seeking medical cannabis certification (either for the first time or as a renewal) at medical cannabis clinics in southern Michigan completed a screening assessment. Participants completed measures of route of cannabis administration, cannabis use, alcohol and other substance use. An estimated 39% (n=511) of the sample reported past-month cannabis vaping, but vaping as the sole route of cannabis administration was rare. Specifically, only 30 participants (2.3% of the full sample and 5.9% of those who reported any vaping) indicated vaping as the sole route of cannabis administration. The majority (87.3%) of those who reported vaping also reported smoking (combustion) as a route of cannabis administration. Being younger than age 44, having more than a high school education, engaging in nonmedical stimulant use, being a returning medical cannabis patient, and greater frequency of cannabis use were associated with higher odds of vaping at the bivariate level and with all variables considered simultaneously. Vaping appears to be relatively common among medical cannabis patients, but is seldom used as the sole route of cannabis administration. highlight the importance of monitoring trends in vaping and other substance use behaviors in this population and underscore the need for longitudinal research into the motives, correlates, and consequences of cannabis vaping in medical cannabis patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Potential dangers of cannabis.

PubMed

Kaymakçalan, S

1975-01-01

Cannabis is not a harmless drug. The potential dangers of cannabis are briefly reviewed in this report. The above-mentioned observations on cannabis users should be kept in mind and carefully examined by all physicians. One could expect that as more potent cannabis preparations become available, some of the toxic manifestations which now seem rare might become more frequent. Some of the remarks about the dangers of cannabis may not be proved in future studies, and they may represent only our anxiety. However, prior to the elimination of these fears, no steps should be taken toward the legalizing of marijuana. At present there is no scientific evidence that cannabis is less harmful than either tobacco or alcohol. The opposite may be true. The analogy can be drawn between opium and cannabis. The permissive attitude toward the use of opium can easily lead to the use of morphine and other opiates. If we legalize the use of marijuana, we cannot prevent the use of more dangerous derivatives of cannabis; namely, hashish, cannabis oil and THC, itself. In my opinion, in the light of our present knowledge, legalizing of marijuana could be hazardous both for the individual and for society.

Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers

PubMed Central

Haney, Margaret; Ramesh, Divya; Glass, Andrew; Pavlicova, Martina; Bedi, Gillinder; Cooper, Ziva D

2015-01-01

Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n=18 M and 5 F) or placebo (0 mg; n=26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4–6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects (‘good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1–51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of ‘good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder. PMID:25881117

Consumer perceptions of strain differences in Cannabis aroma

PubMed Central

DiVerdi, Joseph A.

2018-01-01

The smell of marijuana (Cannabis sativa L.) is of interest to users, growers, plant breeders, law enforcement and, increasingly, to state-licensed retail businesses. The numerous varieties and strains of Cannabis produce strikingly different scents but to date there have been few, if any, attempts to quantify these olfactory profiles directly. Using standard sensory evaluation techniques with untrained consumers we have validated a preliminary olfactory lexicon for dried cannabis flower, and characterized the aroma profile of eleven strains sold in the legal recreational market in Colorado. We show that consumers perceive differences among strains, that the strains form distinct clusters based on odor similarity, and that strain aroma profiles are linked to perceptions of potency, price, and smoking interest. PMID:29401526

Auditory mismatch negativity deficits in long-term heavy cannabis users.

PubMed

Roser, Patrik; Della, Beate; Norra, Christine; Uhl, Idun; Brüne, Martin; Juckel, Georg

2010-09-01

Mismatch negativity (MMN) is an auditory event-related potential indicating auditory sensory memory and information processing. The present study tested the hypothesis that chronic cannabis use is associated with deficient MMN generation. MMN was investigated in age- and gender-matched chronic cannabis users (n = 30) and nonuser controls (n = 30). The cannabis users were divided into two groups according to duration and quantity of cannabis consumption. The MMNs resulting from a pseudorandomized sequence of 2 × 900 auditory stimuli were recorded by 32-channel EEG. The standard stimuli were 1,000 Hz, 80 dB SPL and 90 ms duration. The deviant stimuli differed in duration (50 ms) or frequency (1,200 Hz). There were no significant differences in MMN values between cannabis users and nonuser controls in both deviance conditions. With regard to subgroups, reduced amplitudes of frequency MMN at frontal electrodes were found in long-term (≥8 years of use) and heavy (≥15 joints/week) users compared to short-term and light users. The results indicate that chronic cannabis use may cause a specific impairment of auditory information processing. In particular, duration and quantity of cannabis use could be identified as important factors of deficient MMN generation.

Probability and predictors of the cannabis gateway effect: A national study

PubMed Central

Secades-Villa, Roberto; Garcia-Rodríguez, Olaya; Jin, Chelsea, J.; Wang, Shuai; Blanco, Carlos

2014-01-01

Background While several studies have shown a high association between cannabis use and use of other illicit drugs, the predictors of progression from cannabis to other illicit drugs remain largely unknown. This study aims to estimate the cumulative probability of progression to illicit drug use among individuals with lifetime history of cannabis use, and to identify predictors of progression from cannabis use to other illicit drugs use. Methods Analyses were conducted on the sub-sample of participants in Wave 1of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) who started cannabis use before using any other drug (n= 6,624). Estimated projections of the cumulative probability of progression from cannabis use to use of any other illegal drug use in the general population were obtained by the standard actuarial method. Univariate and multivariable survival analyses with time-varying covariates were implemented to identify predictors of progression to any drug use. Results Lifetime cumulative probability estimates indicated that 44.7% of individuals with lifetime cannabis use progressed to other illicit drug use at some time in their lives. Several sociodemographic characteristics, internalizing and externalizing psychiatric disorders and indicators of substance use severity predicted progression from cannabis use to other illicit drugs use. Conclusion A large proportion of individuals who use cannabis go on to use other illegal drugs. The increased risk of progression from cannabis use to other illicit drugs use among individuals with mental disorders underscores the importance of considering the benefits and adverse effects of changes in cannabis regulations and of developing prevention and treatment strategies directed at curtailing cannabis use in these populations. PMID:25168081

Cannabis, cannabinoids, and health.

PubMed

Lafaye, Genevieve; Karila, Laurent; Blecha, Lisa; Benyamina, Amine

2017-09-01

Cannabis (also known as marijuana) is the most frequently used illicit psychoactive substance in the world. Though it was long considered to be a "soft" drug, studies have proven the harmful psychiatric and addictive effects associated with its use. A number of elements are responsible for the increased complications of cannabis use, including the increase in the potency of cannabis and an evolution in the ratio between the two primary components, Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (toward a higher proportion of Δ 9 -THC), Synthetic cannabinoid (SC) use has rapidly progressed over the last few years, primarily among frequent cannabis users, because SCs provide similar psychoactive effects to cannabis. However, their composition and pharmacological properties make them dangerous substances. Cannabis does have therapeutic properties for certain indications. These therapeutic applications pertain only to certain cannabinoids and their synthetic derivatives. The objective of this article is to summarize current developments concerning cannabis and the spread of SCs. Future studies must further explore the benefit-risk profile of medical cannabis use.

Cannabis, cannabinoids, and health

PubMed Central

Lafaye, Genevieve; Karila, Laurent; Blecha, Lisa; Benyamina, Amine

2017-01-01

Cannabis (also known as marijuana) is the most frequently used illicit psychoactive substance in the world. Though it was long considered to be a “soft” drug, studies have proven the harmful psychiatric and addictive effects associated with its use. A number of elements are responsible for the increased complications of cannabis use, including the increase in the potency of cannabis and an evolution in the ratio between the two primary components, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (toward a higher proportion of Δ9-THC), Synthetic cannabinoid (SC) use has rapidly progressed over the last few years, primarily among frequent cannabis users, because SCs provide similar psychoactive effects to cannabis. However, their composition and pharmacological properties make them dangerous substances. Cannabis does have therapeutic properties for certain indications. These therapeutic applications pertain only to certain cannabinoids and their synthetic derivatives. The objective of this article is to summarize current developments concerning cannabis and the spread of SCs. Future studies must further explore the benefit-risk profile of medical cannabis use. PMID:29302228

Sex Differences in Cannabis Use and Effects: A Cross-Sectional Survey of Cannabis Users

PubMed Central

Cuttler, Carrie; Mischley, Laurie K.; Sexton, Michelle

2016-01-01

Abstract Introduction: Despite known sex differences in the endocannabinoid system of animals, little attention has been paid to sex differences in human's cannabis use patterns and effects. The purpose of the present study was to examine sex differences in cannabis use patterns and effects in a large sample of recreational and medical cannabis users. Methods: A large sample (n=2374) of cannabis users completed an anonymous, online survey that assessed their cannabis use practices and experiences, including the short-term acute effects of cannabis and withdrawal effects. A subsample of 1418 medical cannabis users further indicated the medical conditions for which they use cannabis and its perceived efficacy. Results: The results indicated that men reported using cannabis more frequently and in higher quantities than did women. Men were more likely to report using joints/blunts, vaporizers, and concentrates, while women were more likely to report using pipes and oral administration. Men were more likely than women to report increased appetite, improved memory, enthusiasm, altered time perception, and increased musicality when high, while women were more likely than men to report loss of appetite and desire to clean when high. Men were more likely than women to report insomnia and vivid dreams during periods of withdrawal, while women were more likely than men to report nausea and anxiety as withdrawal symptoms. Sex differences in the conditions for which medical cannabis is used, and its efficacy, were trivial. Conclusions: These results may be used to focus research on biological and psychosocial mechanisms underlying cannabis-related sex differences, to inform clinicians treating individuals with cannabis use disorders, and to inform cannabis consumers, clinicians, and policymakers about the risks and benefits of cannabis for both sexes. PMID:28861492

Sex Differences in Cannabis Use and Effects: A Cross-Sectional Survey of Cannabis Users.

PubMed

Cuttler, Carrie; Mischley, Laurie K; Sexton, Michelle

2016-01-01

Introduction: Despite known sex differences in the endocannabinoid system of animals, little attention has been paid to sex differences in human's cannabis use patterns and effects. The purpose of the present study was to examine sex differences in cannabis use patterns and effects in a large sample of recreational and medical cannabis users. Methods: A large sample ( n =2374) of cannabis users completed an anonymous, online survey that assessed their cannabis use practices and experiences, including the short-term acute effects of cannabis and withdrawal effects. A subsample of 1418 medical cannabis users further indicated the medical conditions for which they use cannabis and its perceived efficacy. Results: The results indicated that men reported using cannabis more frequently and in higher quantities than did women. Men were more likely to report using joints/blunts, vaporizers, and concentrates, while women were more likely to report using pipes and oral administration. Men were more likely than women to report increased appetite, improved memory, enthusiasm, altered time perception, and increased musicality when high, while women were more likely than men to report loss of appetite and desire to clean when high. Men were more likely than women to report insomnia and vivid dreams during periods of withdrawal, while women were more likely than men to report nausea and anxiety as withdrawal symptoms. Sex differences in the conditions for which medical cannabis is used, and its efficacy, were trivial. Conclusions: These results may be used to focus research on biological and psychosocial mechanisms underlying cannabis-related sex differences, to inform clinicians treating individuals with cannabis use disorders, and to inform cannabis consumers, clinicians, and policymakers about the risks and benefits of cannabis for both sexes.

[Epidemiological news in cannabis].

PubMed

Beck, François; Guignard, Romain; Richard, Jean-Baptiste

2013-12-01

Cannabis is by far the most common illicit drug in France. Among 15-64 years, 32.1% have already experienced it and 8.4% declare they have used it at least once during the past twelve months. In Europe, France is one of the countries with the highest prevalence. Males are markedly more often cannabis users than females and this gender gap tends to increase with the level of use. During the last two decades, the part of the population having tried cannabis did not stop increasing, under the influence of a generalization of the cannabis experience among young people. However, cannabis last year prevalence is rather stable since 2000. Cannabis lifetime use is very rare at the beginning of middle school (1.5% in sixth grade at age 11) but increases in the following years (11% of the pupils of the eighth grade, 24% of the pupils of the ninth grade). Cannabis use at a younger age is related to subsequent onset of cannabis related problems. Adolescent and young adults from high socioeconomic status (SES) more often try cannabis than young people from lower SES. However, cannabis regular use is associated with bad school results, truancy and early school leaving, and with a lower SES. Young people from high SES indeed dispose of greater sociocultural resources to master and regulate their consumption and are more often conscious of their interest not to be tipped over in problematic use.

Chronic toxicology of cannabis.

PubMed

Reece, Albert Stuart

2009-07-01

Cannabis is the most widely used illicit drug worldwide. As societies reconsider the legal status of cannabis, policy makers and clinicians require sound knowledge of the acute and chronic effects of cannabis. This review focuses on the latter. A systematic review of Medline, PubMed, PsychInfo, and Google Scholar using the search terms "cannabis," "marijuana," "marihuana," "toxicity," "complications," and "mechanisms" identified 5,198 papers. This list was screened by hand, and papers describing mechanisms and those published in more recent years were chosen preferentially for inclusion in this review. There is evidence of psychiatric, respiratory, cardiovascular, and bone toxicity associated with chronic cannabis use. Cannabis has now been implicated in the etiology of many major long-term psychiatric conditions including depression, anxiety, psychosis, bipolar disorder, and an amotivational state. Respiratory conditions linked with cannabis include reduced lung density, lung cysts, and chronic bronchitis. Cannabis has been linked in a dose-dependent manner with elevated rates of myocardial infarction and cardiac arrythmias. It is known to affect bone metabolism and also has teratogenic effects on the developing brain following perinatal exposure. Cannabis has been linked to cancers at eight sites, including children after in utero maternal exposure, and multiple molecular pathways to oncogenesis exist. Chronic cannabis use is associated with psychiatric, respiratory, cardiovascular, and bone effects. It also has oncogenic, teratogenic, and mutagenic effects all of which depend upon dose and duration of use.

Public opinion and medical cannabis policies: examining the role of underlying beliefs and national medical cannabis policies.

PubMed

Sznitman, Sharon R; Bretteville-Jensen, Anne Line

2015-10-14

Debate about medical cannabis legalization are typically informed by three beliefs: (1) cannabis has medical effects, (2) medical cannabis is addictive and (3) medical cannabis legalization leads to increased used of cannabis for recreational purposes (spillover effects). We examined how strongly these beliefs are associated with public support for medical cannabis legalization and whether this association differs across divergent medical cannabis policy regimes. Robust regression analysis was used to analyse data derived from two nationally representative samples of adults participating in comparable cross-sectional online surveys in one country where medical cannabis smoking is illegal (Norway, n = 2175, 51 % male) and in one country where medical cannabis smoking is legal (Israel, n = 648, 49 % male). The belief that cannabis has medical benefits was more strongly related to support for medical cannabis legalization than were beliefs about addiction and spillover effects. While the support for medical cannabis legalization was stronger in Israel than in Norway (78 vs. 51 %, p < 0.01), the belief variables had, in general, more impact on the policy stand in Norway. The belief that cannabis has medical benefits is particularly salient for support for medical cannabis legalization. It is possible that the recent surge in evidence supporting the medical benefits of cannabis will increase the belief about medical benefits of cannabis in the general population which may in turn increase public support for medical cannabis legalization. Results also suggest that once medical cannabis is legalized, factors beyond cannabis-specific beliefs will increasingly influence medical cannabis legalization support. These conclusions are, however, only suggestive as the current study is based on cross-sectional data. Hopefully, future research will be able to capitalize on changes in medical cannabis policies and conduct longitudinal studies that enable an

Dopaminergic function in cannabis users and its relationship to cannabis-induced psychotic symptoms.

PubMed

Bloomfield, Michael A P; Morgan, Celia J A; Egerton, Alice; Kapur, Shitij; Curran, H Valerie; Howes, Oliver D

2014-03-15

Cannabis is the most widely used illicit drug globally, and users are at increased risk of mental illnesses including psychotic disorders such as schizophrenia. Substance dependence and schizophrenia are both associated with dopaminergic dysfunction. It has been proposed, although never directly tested, that the link between cannabis use and schizophrenia is mediated by altered dopaminergic function. We compared dopamine synthesis capacity in 19 regular cannabis users who experienced psychotic-like symptoms when they consumed cannabis with 19 nonuser sex- and age-matched control subjects. Dopamine synthesis capacity (indexed as the influx rate constant [Formula: see text] ) was measured with positron emission tomography and 3,4-dihydroxy-6-[(18)F]-fluoro-l-phenylalanine ([(18)F]-DOPA). Cannabis users had reduced dopamine synthesis capacity in the striatum (effect size: .85; t36 = 2.54, p = .016) and its associative (effect size: .85; t36 = 2.54, p = .015) and limbic subdivisions (effect size: .74; t36 = 2.23, p = .032) compared with control subjects. The group difference in dopamine synthesis capacity in cannabis users compared with control subjects was driven by those users meeting cannabis abuse or dependence criteria. Dopamine synthesis capacity was negatively associated with higher levels of cannabis use (r = -.77, p < .001) and positively associated with age of onset of cannabis use (r = .51, p = .027) but was not associated with cannabis-induced psychotic-like symptoms (r = .32, p = .19). These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Cannabis Liberalization and Adolescent Cannabis Use: A Cross-National Study in 38 Countries

PubMed Central

Shi, Yuyan; Lenzi, Michela; An, Ruopeng

2015-01-01

Aims To assess the associations between types of cannabis control policies at country level and prevalence of adolescent cannabis use. Setting, Participants and Design Multilevel logistic regressions were performed on 172,894 adolescents 15 year of age who participated in the 2001/2002, 2005/2006, or 2009/2010 cross-sectional Health Behaviour in School-Aged Children (HBSC) survey in 38 European and North American countries. Measures Self-reported cannabis use status was classified into ever use in life time, use in past year, and regular use. Country-level cannabis control policies were categorized into a dichotomous measure (whether or not liberalized) as well as 4 detailed types (full prohibition, depenalization, decriminalization, and partial prohibition). Control variables included individual-level sociodemographic characteristics and country-level economic characteristics. Findings Considerable intra-class correlations (.15-.19) were found at country level. With respect to the dichotomized cannabis control policy, adolescents were more likely to ever use cannabis (odds ratio (OR) = 1.10, p = .001), use in past year (OR = 1.09, p = .007), and use regularly (OR = 1.26, p = .004). Although boys were substantially more likely to use cannabis, the correlation between cannabis liberalization and cannabis use was smaller in boys than in girls. With respect to detailed types of policies, depenalization was associated with higher odds of past-year use (OR = 1.14, p = .013) and regular use (OR = 1.23, p = .038), and partial prohibition was associated with higher odds of regular use (OR = 2.39, p = .016). The correlation between cannabis liberalization and regular use was only significant after the policy had been introduced for more than 5 years. Conclusions Cannabis liberalization with depenalization and partial prohibition policies was associated with higher levels of regular cannabis use among adolescents. The correlations were heterogeneous between genders and

Can we make cannabis safer?

PubMed

Englund, Amir; Freeman, Tom P; Murray, Robin M; McGuire, Philip

2017-08-01

Cannabis use and related problems are on the rise globally alongside an increase in the potency of cannabis sold on both black and legal markets. Additionally, there has been a shift towards abandoning prohibition for a less punitive and more permissive legal stance on cannabis, such as decriminalisation and legalisation. It is therefore crucial that we explore new and innovative ways to reduce harm. Research has found cannabis with high concentrations of its main active ingredient, δ-9-tetrahydrocannabinol (THC), to be more harmful (in terms of causing the main risks associated with cannabis use, such as addiction, psychosis, and cognitive impairment) than cannabis with lower concentrations of THC. By contrast, cannabidiol, which is a non-intoxicating and potentially therapeutic component of cannabis, has been found to reduce the negative effects of cannabis use. Here, we briefly review findings from studies investigating various types of cannabis and discuss how future research can help to better understand and reduce the risks of cannabis use. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cannabis-based medicines--GW pharmaceuticals: high CBD, high THC, medicinal cannabis--GW pharmaceuticals, THC:CBD.

PubMed

2003-01-01

conditions: pain in spinal cord injury, pain and sleep in MS and spinal cord injury, neuropathic pain in MS and general neuropathic pain (presented as allodynia). Results from these trials show that THC:CBD (narrow ratio) caused statistically significant reductions in neuropathic pain in patients with MS and other conditions. In addition, improvements in other MS symptoms were observed as well. Phase II studies of THC:CBD (narrow ratio) have also been completed in patients with MS, spinal cord injury, neuropathic pain and a small number of patients with peripheral neuropathy secondary to diabetes mellitus or AIDS. A phase II trial of THC:CBD (broad ratio) has also been completed in a small number of patients with rheumatoid arthritis, as has a trial of High CBD in patients with neurogenic symptoms. A phase II trial has also been evaluated with High THC in small numbers of patients for the treatment of perioperative pain. The phase II trials provided positive results and confirmed an excellent safety profile for cannabis-based medicines. GW Pharmaceuticals received an IND approval to commence phase II clinical trials in Canada in patients with chronic pain, multiple sclerosis and spinal cord injury in 2002. Following meetings with the US FDA, Drug Enforcement Agency (DEA), the Office for National Drug Control Policy, and National Institute for Drug Abuse, GW was granted an import license from the DEA and has imported its first cannabis extracts into the US. Preclinical research with these extracts in the US is ongoing.

When Cannabis Is Available and Visible at School--A Multilevel Analysis of Students' Cannabis Use

ERIC Educational Resources Information Center

Kuntsche, Emmanuel

2010-01-01

Aims: To investigate the links between the visibility of cannabis use in school (measured by teachers' reports of students being under the influence of cannabis on school premises), the proportion of cannabis users in the class, perceived availability of cannabis, as well as adolescent cannabis use. Methods: A multilevel regression model was…

Prevalence and Correlates of “Vaping” as a Route of Cannabis Administration in Medical Cannabis Patients

PubMed Central

Cranford, James A.; Bohnert, Kipling M.; Perron, Brian E.; Bourque, Carrie; Ilgen, Mark

2016-01-01

Purpose To examine the prevalence and correlates of vaporization (i.e., “vaping”) as a route of cannabis administration in a sample of medical cannabis patients. Procedures Adults ages 21 and older (N = 1,485 M age = 45.1) who were seeking medical cannabis certification (either for the first time or as a renewal) at medical cannabis clinics in southern Michigan completed a screening assessment. Participants completed measures of route of cannabis administration, cannabis use, alcohol and other substance use. Findings An estimated 39% (n=511) of the sample reported past-month cannabis vaping, but vaping as the sole route of cannabis administration was rare. Specifically, only 30 participants (2.3% of the full sample and 5.9% of those who reported any vaping) indicated vaping as the sole route of cannabis administration. The majority (87.3%) of those who reported vaping also reported smoking (combustion) as a route of cannabis administration. Being younger than age 44, having more than a high school education, engaging in nonmedical stimulant use, being a returning medical cannabis patient, and greater frequency of cannabis use were associated with higher odds of vaping at the bivariate level and with all variables considered simultaneously. Conclusions Vaping appears to be relatively common among medical cannabis patients, but is seldom used as the sole route of cannabis administration. Results highlight the importance of monitoring trends in vaping and other substance use behaviors in this population and underscore the need for longitudinal research into the motives, correlates, and consequences of cannabis vaping in medical cannabis patients. PMID:27770657

Cannabis Problem Experiences Among Users of the Tobacco-Cannabis Combination Known As Blunts

PubMed Central

Fairman, Brian J.

2015-01-01

Background In most of the world, cannabis smokers mix loose tobacco inside a joint, pipe, spliff, or cone. More recently, a ‘blunt’ formulation combines these two drugs by inserting cannabis into a hollowed-out cigar. Epidemiological research linking simultaneous use of these two drugs and the development of cannabis use disorders (CUD) remains unclear. This study estimates associations linking blunt smoking with levels and subtypes of cannabis problems. Methods Cross-sectional data on 27,767 past-year cannabis users were analyzed from the US National Survey on Drug Use and Health (NSDUH) conducted from 2009–2012. Ten self-reported items of DSM-IV CUD features elicited a single latent trait of cannabis problem (CP) severity, which was then regressed on past-year blunt smoking and past-month blunt frequency measures within the context of a conceptual model. Differential item functioning (DIF) analysis evaluated potential bias in CP feature response by blunt smoking history. Results Past-year blunt smoking was associated with higher CP severity compared to cannabis users who did not smoke blunts. Days of blunt smoking in the past month also predicted higher CP severity than less frequent blunt use. Those smoking blunts experienced more subjectively felt tolerance and having spent more time obtaining or using cannabis, but were less likely to experience other problems, even at the same level of CP severity. Conclusions These findings suggest smoking blunts might promote the development of problematic cannabis use. Responses to cannabis problems differed by history of blunt smoking, possibly implicating an influence of tobacco on measurement of cannabis use disorders. PMID:25746234

Cannabis problem experiences among users of the tobacco-cannabis combination known as blunts.

PubMed

Fairman, Brian J

2015-05-01

In most of the world, cannabis smokers mix loose tobacco inside a joint, pipe, spliff, or cone. More recently, a 'blunt' formulation combines these two drugs by inserting cannabis into a hollowed-out cigar. Epidemiological research linking simultaneous use of these two drugs and the development of cannabis use disorders (CUD) remains unclear. This study estimates associations linking blunt smoking with levels and subtypes of cannabis problems. Cross-sectional data on 27,767 past-year cannabis users were analyzed from the US National Survey on Drug Use and Health (NSDUH) conducted from 2009 to 2012. Ten self-reported items of DSM-IV CUD features elicited a single latent trait of cannabis problem (CP) severity, which was then regressed on past-year blunt smoking and past-month blunt frequency measures within the context of a conceptual model. Differential item functioning (DIF) analysis evaluated potential bias in CP feature response by blunt smoking history. Past-year blunt smoking was associated with higher CP severity compared to cannabis users who did not smoke blunts. Days of blunt smoking in the past month also predicted higher CP severity than less frequent blunt use. Those smoking blunts experienced more subjectively felt tolerance and having spent more time obtaining or using cannabis, but were less likely to experience other problems, even at the same level of CP severity. These findings suggest smoking blunts might promote the development of problematic cannabis use. Responses to cannabis problems differed by history of blunt smoking, possibly implicating an influence of tobacco on measurement of cannabis use disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Sex differences in associations between cannabis craving and neural responses to cannabis cues: Implications for treatment.

PubMed

Wetherill, Reagan R; Jagannathan, Kanchana; Hager, Nathan; Childress, Anna Rose; Franklin, Teresa R

2015-08-01

Preclinical and clinical research indicates that there are sex differences in how men and women initiate, progress, respond to, and withdraw from cannabis use; however, neurophysiological differences, such as neural responses to cannabis cues, are not well understood. Using functional MRI and an event-related blood oxygen level-dependent backward-masking task, we compared neural responses to backward-masked cannabis cues to neutral cues in treatment-seeking, cannabis-dependent adults (N = 44; 27 males) and examined whether sex differences exist. In addition, functional MRI findings were correlated with cannabis craving. Backward-masked cannabis cues elicited greater neural responses than neutral cues in reward-related brain regions, including the striatum, hippocampus/amygdala, insula, anterior cingulate cortex, and lateral orbitofrontal cortex, p < .01, k > 121 voxels. Although no significant sex differences in neural responses to cannabis cues emerged, women showed a positive correlation between neural responses to cannabis cues in the bilateral insula and cannabis craving and an inverse correlation between neural responses to cannabis cues in the left lateral orbitofrontal cortex and cannabis craving. Men, however, showed a positive correlation between neural responses to cannabis cues in the striatum and cannabis craving. Given that cues and craving are important triggers and the focus on many behavioral treatment approaches, these findings suggest that treatment-seeking, cannabis-dependent men and women may benefit from sex-specific and tailored cannabis use disorder treatments. (c) 2015 APA, all rights reserved).

Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study.

PubMed

Carroll, C B; Bain, P G; Teare, L; Liu, X; Joint, C; Wroath, C; Parkin, S G; Fox, P; Wright, D; Hobart, J; Zajicek, J P

2004-10-12

The long-term treatment of Parkinson disease (PD) may be complicated by the development of levodopa-induced dyskinesia. Clinical and animal model data support the view that modulation of cannabinoid function may exert an antidyskinetic effect. The authors conducted a randomized, double-blind, placebo-controlled crossover trial to examine the hypothesis that cannabis may have a beneficial effect on dyskinesia in PD. A 4-week dose escalation study was performed to assess the safety and tolerability of cannabis in six PD patients with levodopa-induced dyskinesia. Then a randomized placebo-controlled crossover study (RCT) was performed, in which 19 PD patients were randomized to receive oral cannabis extract followed by placebo or vice versa. Each treatment phase lasted for 4 weeks with an intervening 2-week washout phase. The primary outcome measure was a change in Unified Parkinson's Disease Rating Scale (UPDRS) (items 32 to 34) dyskinesia score. Secondary outcome measures included the Rush scale, Bain scale, tablet arm drawing task, and total UPDRS score following a levodopa challenge, as well as patient-completed measures of a dyskinesia activities of daily living (ADL) scale, the PDQ-39, on-off diaries, and a range of category rating scales. Seventeen patients completed the RCT. Cannabis was well tolerated, and had no pro- or antiparkinsonian action. There was no evidence for a treatment effect on levodopa-induced dyskinesia as assessed by the UPDRS, or any of the secondary outcome measures. Orally administered cannabis extract resulted in no objective or subjective improvement in dyskinesias or parkinsonism.

Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

PubMed Central

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-01-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

Self-medication of achalasia with cannabis, complicated by a cannabis use disorder.

PubMed

Luquiens, Amandine; Lourenco, Nelson; Benyamina, Amine; Aubin, Henri-Jean

2015-05-28

Achalasia is a rare esophagus motility disorder. Medical, endoscopic and surgical treatments are available, but all endorse high relapse rates. No data has been published to date reporting a therapeutic effect of cannabis use neither in achalasia nor on its influence on manometric measurements. We report the case of a patient diagnosed with achalasia. He could benefit from a large panel of therapeutic interventions, but none of them was effective over the time. He first used cannabis at age 20 and identified benefits regarding achalasia symptoms. He maintained regular moderate cannabis use for 9 years, with minimal digestive inconvenience. A manometry performed without cannabis premedication was realized at age 26 and still found a cardiospasm. Cannabis use could explain the gap between functional symptoms assessment and manometry measurement. Further investigations are warranted to explore a therapeutic effect of cannabis in achalasia and possible influence on outcome measurements.

Examining the profile of high-potency cannabis and its association with severity of cannabis dependence.

PubMed

Freeman, T P; Winstock, A R

2015-11-01

Cannabis use is decreasing in England and Wales, while demand for cannabis treatment in addiction services continues to rise. This could be partly due to an increased availability of high-potency cannabis. Adults residing in the UK were questioned about their drug use, including three types of cannabis (high potency: skunk; low potency: other grass, resin). Cannabis types were profiled and examined for possible associations between frequency of use and (i) cannabis dependence, (ii) cannabis-related concerns. Frequent use of high-potency cannabis predicted a greater severity of dependence [days of skunk use per month: b = 0.254, 95% confidence interval (CI) 0.161-0.357, p < 0.001] and this effect became stronger as age decreased (b = -0.006, 95% CI -0.010 to -0.002, p = 0.004). By contrast, use of low-potency cannabis was not associated with dependence (days of other grass use per month: b = 0.020, 95% CI -0.029 to 0.070, p = 0.436; days of resin use per month: b = 0.025, 95% CI -0.019 to 0.067, p = 0.245). Frequency of cannabis use (all types) did not predict severity of cannabis-related concerns. High-potency cannabis was clearly distinct from low-potency varieties by its marked effects on memory and paranoia. It also produced the best high, was preferred, and most available. High-potency cannabis use is associated with an increased severity of dependence, especially in young people. Its profile is strongly defined by negative effects (memory, paranoia), but also positive characteristics (best high, preferred type), which may be important when considering clinical or public health interventions focusing on cannabis potency.

Psychosocial functioning among regular cannabis users with and without cannabis use disorder.

PubMed

Foster, Katherine T; Arterberry, Brooke J; Iacono, William G; McGue, Matt; Hicks, Brian M

2017-11-27

In the United States, cannabis accessibility has continued to rise as the perception of its harmfulness has decreased. Only about 30% of regular cannabis users develop cannabis use disorder (CUD), but it is unclear if individuals who use cannabis regularly without ever developing CUD experience notable psychosocial impairment across the lifespan. Therefore, psychosocial functioning was compared across regular cannabis users with or without CUD and a non-user control group during adolescence (age 17; early risk) and young adulthood (ages 18-25; peak CUD prevalence). Weekly cannabis users with CUD (n = 311), weekly users without CUD (n = 111), and non-users (n = 996) were identified in the Minnesota Twin Family Study. Groups were compared on alcohol and illicit drug use, psychiatric problems, personality, and social functioning at age 17 and from ages 18 to 25. Self-reported cannabis use and problem use were independently verified using co-twin informant report. In both adolescence and young adulthood, non-CUD users reported significantly higher levels of substance use problems and externalizing behaviors than non-users, but lower levels than CUD users. High agreement between self- and co-twin informant reports confirmed the validity of self-reported cannabis use problems. Even in the absence of CUD, regular cannabis use was associated with psychosocial impairment in adolescence and young adulthood. However, regular users with CUD endorsed especially high psychiatric comorbidity and psychosocial impairment. The need for early prevention and intervention - regardless of CUD status - was highlighted by the presence of these patterns in adolescence.

Extract of Fructus Cannabis Ameliorates Learning and Memory Impairment Induced by D-Galactose in an Aging Rats Model.

PubMed

Chen, Ning-Yuan; Liu, Cheng-Wu; Lin, Wei; Ding, Yi; Bian, Zhang-Ya; Huang, Ling; Huang, Hao; Yu, Kai-Hui; Chen, Si-Bang; Sun, Yu; Wei, Lei; Peng, Jun-Hua; Pan, Shang-Ling

2017-01-01

Hempseed ( Cannabis sativa L.) has been used as a health food and folk medicine in China for centuries. In the present study, we sought to define the underlying mechanism by which the extract of Fructus Cannabis (EFC) protects against memory impairment induced by D-galactose in rats. To accelerate aging and induce memory impairment in rats, D-galactose (400 mg/kg) was injected intraperitoneally once daily for 14 weeks. EFC (200 and 400 mg/kg) was simultaneously administered intragastrically once daily in an attempt to slow the aging process. We found that EFC significantly increased the activity of superoxide dismutase, while lowering levels of malondialdehyde in the hippocampus. Moreover, EFC dramatically elevated the organ indices of some organs, including the heart, the liver, the thymus, and the spleen. In addition, EFC improved the behavioral performance of rats treated with D-galactose in the Morris water maze. Furthermore, EFC inhibited the activation of astrocytes and remarkably attenuated phosphorylated tau and suppressed the expression of presenilin 1 in the brain of D-galactose-treated rats. These findings suggested that EFC exhibits beneficial effects on the cognition of aging rats probably by enhancing antioxidant capacity and anti-neuroinflammation, improving immune function, and modulating tau phosphorylation and presenilin expression.

Cannabis, motivation, and life satisfaction in an internet sample

PubMed Central

Barnwell, Sara Smucker; Earleywine, Mitch; Wilcox, Rand

2006-01-01

Although little evidence supports cannabis-induced amotivational syndrome, sources continue to assert that the drug saps motivation [1], which may guide current prohibitions. Few studies report low motivation in chronic users; another reveals that they have higher subjective wellbeing. To assess differences in motivation and subjective wellbeing, we used a large sample (N = 487) and strict definitions of cannabis use (7 days/week) and abstinence (never). Standard statistical techniques showed no differences. Robust statistical methods controlling for heteroscedasticity, non-normality and extreme values found no differences in motivation but a small difference in subjective wellbeing. Medical users of cannabis reporting health problems tended to account for a significant portion of subjective wellbeing differences, suggesting that illness decreased wellbeing. All p-values were above p = .05. Thus, daily use of cannabis does not impair motivation. Its impact on subjective wellbeing is small and may actually reflect lower wellbeing due to medical symptoms rather than actual consumption of the plant. PMID:16722561

The Cannabis Withdrawal Scale development: patterns and predictors of cannabis withdrawal and distress.

PubMed

Allsop, David J; Norberg, Melissa M; Copeland, Jan; Fu, Shanlin; Budney, Alan J

2011-12-01

Rates of treatment seeking for cannabis are increasing, and relapse is common. Management of cannabis withdrawal is an important intervention point. No psychometrically sound measure for cannabis withdrawal exists, and as a result treatment developments cannot be optimally targeted. The aim is to develop and test the psychometrics of the Cannabis Withdrawal Scale and use it to explore predictors of cannabis withdrawal. A volunteer sample of 49 dependent cannabis users provided daily scores on the Cannabis Withdrawal Scale during a baseline week and 2 weeks of abstinence. Internal reliability (Cronbach's alpha=0.91), test-retest stability (average intra-class correlation=0.95) and content validity analysis show that the Cannabis Withdrawal Scale has excellent psychometric properties. Nightmares and/or strange dreams was the most valid item (Wald χ²=105.6, P<0.0001), but caused relatively little associated distress (Wald χ²=25.11, P=0.03). Angry outbursts were considered intense (Wald χ²=73.69, P<0.0001) and caused much associated distress (Wald χ²=45.54, P<0.0001). Trouble getting to sleep was also an intense withdrawal symptom (Wald χ²=42.31, P<0.0001) and caused significant associated distress (Wald χ²=47.76, P<0.0001). Scores on the Severity of Dependence Scale predicted cannabis withdrawal. The Cannabis Withdrawal Scale can be used as a diagnostic instrument in clinical and research settings where regular monitoring of withdrawal symptoms is required. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Cannabis effects on driving skills.

PubMed

Hartman, Rebecca L; Huestis, Marilyn A

2013-03-01

Cannabis is the most prevalent illicit drug identified in impaired drivers. The effects of cannabis on driving continue to be debated, making prosecution and legislation difficult. Historically, delays in sample collection, evaluating the inactive Δ(9)-tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-THC, and polydrug use have complicated epidemiologic evaluations of driver impairment after cannabis use. We review and evaluate the current literature on cannabis' effects on driving, highlighting the epidemiologic and experimental data. Epidemiologic data show that the risk of involvement in a motor vehicle accident (MVA) increases approximately 2-fold after cannabis smoking. The adjusted risk of driver culpability also increases substantially, particularly with increased blood THC concentrations. Studies that have used urine as the biological matrix have not shown an association between cannabis and crash risk. Experimental data show that drivers attempt to compensate by driving more slowly after smoking cannabis, but control deteriorates with increasing task complexity. Cannabis smoking increases lane weaving and impaired cognitive function. Critical-tracking tests, reaction times, divided-attention tasks, and lane-position variability all show cannabis-induced impairment. Despite purported tolerance in frequent smokers, complex tasks still show impairment. Combining cannabis with alcohol enhances impairment, especially lane weaving. Differences in study designs frequently account for inconsistencies in results between studies. Participant-selection bias and confounding factors attenuate ostensible cannabis effects, but the association with MVA often retains significance. Evidence suggests recent smoking and/or blood THC concentrations 2-5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Future cannabis-and-driving research should emphasize challenging tasks, such as divided attention, and include occasional and

A review of methods for the chemical characterization of cannabis natural products.

PubMed

Leghissa, Allegra; Hildenbrand, Zacariah L; Schug, Kevin A

2018-01-01

Cannabis has garnered a great deal of new attention in the past couple of years in the United States due to the increasing instances of its legalization for recreational use and indications for medicinal benefit. Despite a growing number of laboratories focused on cannabis analysis, the separation science literature pertaining to the determination of cannabis natural products is still in its infancy despite the plant having been utilized by humans for nearly 30 000 years and it being now the most widely used drug worldwide. This is largely attributable to the restrictions associated with cannabis as it is characterized as a schedule 1 drug in the United States. Presented here are reviewed analytical methods for the determination of cannabinoids (primarily) and terpenes (secondarily), the primary natural products of interest in cannabis plants. Focus is placed foremost on analyses from plant extracts and the various instrumentation and techniques that are used, but some coverage is also given to analysis of cannabinoid metabolites found in biological fluids. The goal of this work is to provide a collection of relevant separation science information, upon which the field of cannabis analysis can continue to grow. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The role of general parenting and cannabis-specific parenting practices in adolescent cannabis and other illicit drug use.

PubMed

Vermeulen-Smit, E; Verdurmen, J E E; Engels, R C M E; Vollebergh, W A M

2015-02-01

To investigate general and cannabis-specific parenting practices in relation to adolescent cannabis and other illicit drug use. Data were derived from the Dutch National School Survey on Substance Use among students (N=3209; aged 12-16 years) and one of their parents in 2011. Logistic regression analyses revealed that 1) parental cannabis use was significantly related to more adolescent lifetime and recent cannabis use, and 2) restrictive cannabis-specific parental rules were associated with less adolescent recent cannabis and lifetime use of other illicit drugs, even when controlled for sociodemographic factors, general parenting, adolescent tobacco use, and tobacco-specific parenting. In addition, no significant interaction was observed between parental cannabis use and cannabis-specific rules in their relation to adolescent cannabis and other illicit drug use, indicating that cannabis rules are evenly associated with adolescent drug use for families with and without parental cannabis experience. In addition to general parenting practices, restrictive cannabis-specific rules are related to lower adolescent cannabis and other illicit drug rates. Parents who ever used cannabis have children with a higher prevalence of cannabis use. However, their restrictive cannabis-specific rules are equally related to a lower chance of adolescent cannabis use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Development of a novel immunoassay for herbal cannabis using a new fluorescent antibody probe, "Ultra Quenchbody".

PubMed

Tsujikawa, Kenji; Saiki, Fujio; Yamamuro, Tadashi; Iwata, Yuko T; Abe, Ryoji; Ohashi, Hiroyuki; Kaigome, Rena; Yamane, Kyosuke; Kuwayama, Kenji; Kanamori, Tatsuyuki; Inoue, Hiroyuki

2016-09-01

We developed a novel immunoassay for herbal cannabis based on a new immunoassay principle that uses Ultra Quenchbody ("UQ-body"), a recombinant antibody Fab fragment fluorolabeled at the N-terminal regions. When the antigen binds to anti-Δ(9)-tetrahydrocannabinol (THC) UQ-body, the fluorescence intensity (FI) decreases. The analytical conditions of the immunoassay were optimized based on the FI reduction rate (FIRR). Following are the steps in the final analytical procedure: (1) 10mg of samples were extracted with 1ml of a 60:40 mixture of methanol and phosphate-buffered saline (PBS); (2) the extract was filtered through a centrifugal 0.2-μm polytetrafluoroethylene membrane filter; (3) the filtrate was diluted 100 times with extraction solvent; (4) 6-μl diluted solution was mixed with 19-μl PBS and 75-μl UQ-body solution; and (5) FIRR was measured under 275-mV excitation light. Herbal cannabis samples containing ≥4.0-mg/g THC gave FIRRs of ≥5.2%. FIRRs of negative samples (cigarette, tea, spice, and so-called "synthetic marijuana") were ≤3.1%. When setting the FIRR threshold to 5.0%, cannabis samples containing ≥4.0-mg/g THC were correctly judged as positive without being affected by false positives caused by the negative samples. This detection limit was lower than total THC level (10-200mg/g) in most herbal cannabis samples seized in Japan. In seven of the 10 cannabis samples, the results of the UQ-body test were comparable with those of the Duquenois-Levine test. Thus, the UQ-body-based immunoassay is presumed to be an effective and objective drug screening method for herbal cannabis; however, to show the true usefulness, it is necessary to test a number of real case samples in the field situation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Cannabis and cannabinoids. Possibilities of their therapeutic use].

PubMed

Heim, M E

1982-03-04

Newer aspects of therapeutic potentials of cannabis and cannabinoids are reviewed. The major active constituent of cannabis sativa, delta-9-tetrahydrocannabinol and synthetic cannabinoids are evaluated in several clinical trials on their antiemetic efficacy in cancer chemotherapy induced vomiting. 80% of patients refractory to standard antiemetic treatment could be improved with the synthetic cannabinoid levonantradol. Other therapeutic effects, which are presently investigated in clinical trials are analgesia, antispasticity, anticonvulsion and the reduction of intraocular pressure in glaucoma. The future goal of cannabinoid research is the separation between specific pharmacologic activities and undesirable psychotropic effects.

Cannabis Smoking in 2015

PubMed Central

Biehl, Jason R.

2015-01-01

Recent legislative successes allowing expanded access to recreational and medicinal cannabis have been associated with its increased use by the public, despite continued debates regarding its safety within the medical and scientific communities. Despite legislative changes, cannabis is most commonly used by smoking, although alternatives to inhalation have also emerged. Moreover, the composition of commercially available cannabis has dramatically changed in recent years. Therefore, developing sound scientific information regarding its impact on lung health is imperative, particularly because published data conducted prior to widespread legalization are conflicting and inconclusive. In this commentary, we delineate major observations of epidemiologic investigations examining cannabis use and the potential associated development of airways disease and lung cancer to highlight gaps in pulmonary knowledge. Additionally, we review major histopathologic alterations related to smoked cannabis and define specific areas in animal models and human clinical translational investigations that could benefit from additional development. Given that cannabis has an ongoing classification as a schedule I medication, federal funding to support investigations of modern cannabis use in terms of medicinal efficacy and safety profile on lung health have been elusive. It is clear, however, that the effects of inhaled cannabis on lung health remain uncertain and given increasing use patterns, are worthy of further investigation. PMID:25996274

Effect of hydrolysis on identifying prenatal cannabis exposure

PubMed Central

Gray, Teresa R.; Barnes, Allan J.

2011-01-01

Identification of prenatal cannabis exposure is important due to potential cognitive and behavioral consequences. A two-dimensional gas chromatography–mass spectrometry method for cannabinol, Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 8β,11-dihydroxy-THC, and 11-nor-9-carboxy-THC (THCCOOH) quantification in human meconium was developed and validated. Alkaline, enzymatic, and enzyme–alkaline tandem hydrolysis conditions were optimized with THC- and THCCOOH-glucuronide reference standards. Limits of quantification ranged from 10 to 15 ng/g, and calibration curves were linear to 500 ng/g. Bias and intra-day and inter-day imprecision were <12.3%. Hydrolysis efficiencies were analyte-dependent; THC-glucuronide was effectively cleaved by enzyme, but not base. Conversely, THCCOOH-glucuronide was most sensitive to alkaline hydrolysis. Enzyme–alkaline tandem hydrolysis maximized efficiency for both glucuronides. Identification of cannabinoid-positive meconium specimens nearly doubled following alkaline and enzyme–alkaline hydrolysis. Although no 11-OH-THC glucuronide standard is available, enzymatic hydrolysis improved 11-OH-THC detection in authentic specimens. Maximal identification of cannabis-exposed neonates and the widest range of cannabis biomarkers are achieved with enzyme–alkaline tandem hydrolysis. PMID:20517601

76 FR 39039 - Establishment of a New Drug Code for Marihuana Extract

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-05

... that have been derived from any plant of the genus cannabis and which contain cannabinols and... Nations Conventions on international drug control treat extracts from the cannabis plant differently than.... Cannabis and cannabis resin are listed in both schedule IV and schedule I of the Single Convention...

Estimating the economic value of British Columbia's domestic cannabis market: implications for provincial cannabis policy.

PubMed

Werb, Dan; Nosyk, Bohdan; Kerr, Thomas; Fischer, Benedikt; Montaner, Julio; Wood, Evan

2012-11-01

British Columbia (BC), Canada, is home to a large illegal cannabis industry that is known to contribute to substantial organized crime concerns. Although debates have emerged regarding the potential benefits of a legally regulated market to address a range of drug policy-related social problems, the value of the local (i.e., domestically consumed) cannabis market has not been characterized. Monte Carlo simulation methods were used to generate a median value and 95% credibility interval for retail expenditure estimates of the domestic cannabis market in BC. Model parameter estimates were obtained for the number of cannabis users, the frequency of cannabis use, the quantity of cannabis used, and the price of cannabis from government surveillance data and studies of BC cannabis users. The median annual estimated retail expenditure on cannabis by British Columbians was $407 million (95% Credibility Interval [CI]: $169-948 million). Daily users accounted for the bulk of the cannabis revenue, with a median estimated expenditure of approximately $357 million (95% CI: $149-845 million), followed by weekly users ($44 million, 95% CI: $18-90 million), and monthly users ($6 million, 95% CI: $3-12 million). When under-reporting of cannabis use was adjusted for, the estimated retail expenditure ranged from $443 million (95% CI: $185-1 billion) to $564 million (95% CI: $236-1.3 billion). Based on local consumption patterns, conservative estimates suggest that BC's domestic illegal cannabis trade is worth hundreds of millions of dollars annually. Given the value of this market and the failure and harms of law enforcement efforts to control the cannabis market, policymakers should consider regulatory alternatives. Copyright © 2012 Elsevier B.V. All rights reserved.

Consumer agency in cannabis supply - Exploring auto-regulatory documents of the cannabis social clubs in Spain.

PubMed

Belackova, Vendula; Wilkins, Chris

2018-04-01

There is growing experience with the not-for-profit, consumer-driven cannabis social club (CSC) model that builds on self-supply, self-organization and harm-reduction; these are principles upon which people who use drugs (PWUD) have been engaging for decades. Recent legalization of cannabis in a number of jurisdictions and the related challenges in regulating production, sale, taxation and health-related matters have raised interest in non-commercial models of cannabis supply. The "codes of conduct" (CsoC) of CSC federations in Spain might reveal whether a consumer-based model could overcome these challenges. To examine the content of the CSC auto-regulatory documents, an online search using key terms to identify the CsoC was conducted. Six documents were found; analysis of the main thematic categories and overarching themes was conducted. It was discussed how these corresponded to the areas of cannabis policy regulation and what the main limitations of the CSC model were. The CsoC detailed the rules for CSC administration, not-for-profit aims, "invitation only" and other conditions of membership, collective cultivation and security as well as for operation of the consumption venue and health-related initiatives. The themes in the CsoC overlapped with cannabis regulatory areas as outlined internationally. Concern over cannabis prices and potency was missing in the CsoC. The potential strengths of the CSC model might include safe environment for peer-delivered harm reduction practice, preventing illicit transactions, quality control, shifting economic surplus to the consumers and increased consumer responsibility. The limitations of the CSC model include high threshold, disguised motives, tax revenue and the risk of both under- and over-regulation. CSCs represent an opportunity to enhance consumer agency and responsibility. The right "to be self-supplied" with psychoactive substances can be granted to consumer associations - but authorities need to provide a

Cannabis Use Patterns and Motives: A Comparison of Younger, Middle-Aged, and Older Medical Cannabis Dispensary Patients

PubMed Central

Haug, Nancy A.; Padula, Claudia B.; Sottile, James E.; Vandrey, Ryan; Heinz, Adrienne J.; Bonn-Miller, Marcel O.

2017-01-01

Introduction Medical cannabis is increasingly being used for a variety of health conditions as more states implement legislation permitting medical use of cannabis. Little is known about medical cannabis use patterns and motives among adults across the lifespan. Methods The present study examined data collected at a medical cannabis dispensary in San Francisco, California. Participants included 217 medical cannabis patients who were grouped into age-defined cohorts (younger: 18–30, middle-aged: 31–50, and older: 51–72). The age groups were compared on several measures of cannabis use, motives and medical conditions using one-way ANOVAs, chi-square tests and linear regression analyses. Results All three age groups had similar frequency of cannabis use over the past month; however, the quantity of cannabis used and rates of problematic cannabis use were higher among younger users relative to middle-aged and older adults. The association between age and problematic cannabis use was moderated by age of regular use initiation such that earlier age of regular cannabis use onset was associated with more problematic use in the younger users, but not among older users. Middle-aged adults were more likely to report using medical cannabis for insomnia, while older adults were more likely to use medical cannabis for chronic medical problems such as cancer, glaucoma and HIV/AIDS. Younger participants reported cannabis use when bored at a greater rate than middle-aged and older adults. Conclusions Findings suggest that there is an age-related risk for problematic cannabis use among medical cannabis users, such that younger users should be monitored for cannabis use patterns that may lead to deleterious consequences. PMID:28340421

Cannabis use patterns and motives: A comparison of younger, middle-aged, and older medical cannabis dispensary patients.

PubMed

Haug, Nancy A; Padula, Claudia B; Sottile, James E; Vandrey, Ryan; Heinz, Adrienne J; Bonn-Miller, Marcel O

2017-09-01

Medical cannabis is increasingly being used for a variety of health conditions as more states implement legislation permitting medical use of cannabis. Little is known about medical cannabis use patterns and motives among adults across the lifespan. The present study examined data collected at a medical cannabis dispensary in San Francisco, California. Participants included 217 medical cannabis patients who were grouped into age-defined cohorts (younger: 18-30, middle-aged: 31-50, and older: 51-72). The age groups were compared on several measures of cannabis use, motives and medical conditions using one-way ANOVAs, chi-square tests and linear regression analyses. All three age groups had similar frequency of cannabis use over the past month; however, the quantity of cannabis used and rates of problematic cannabis use were higher among younger users relative to middle-aged and older adults. The association between age and problematic cannabis use was moderated by age of regular use initiation such that earlier age of regular cannabis use onset was associated with more problematic use in the younger users, but not among older users. Middle-aged adults were more likely to report using medical cannabis for insomnia, while older adults were more likely to use medical cannabis for chronic medical problems such as cancer, glaucoma and HIV/AIDS. Younger participants reported cannabis use when bored at a greater rate than middle-aged and older adults. Findings suggest that there is an age-related risk for problematic cannabis use among medical cannabis users, such that younger users should be monitored for cannabis use patterns that may lead to deleterious consequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Medicinal use of cannabis in the Netherlands: towards a responsible pattern of use].

PubMed

de Jong, Floris A

2009-01-01

Since 2003, medicinal cannabis has been legally cultivated and distributed in the Netherlands under the auspices of the Dutch Office of Medicinal Cannabis (BMC), part of the Ministry of Health, Welfare and Sport. As a result of this measure, the indication, dosage, administration route, and safety of cannabis can now be investigated, information necessary for justifying its potentially future position as a standard medicinal product. Despite the current lack of reliable scientific efficacy data, standardised medicinal cannabis without microbes has also been made available on prescription. This has led to a safer and more responsible use. However, it is a bridge too far to say that 'it doesn't hurt to try'. The legalization of medicinal cannabis has also stimulated the development of new purified cannabis-based products, although it is claimed that some patients specifically benefit from using cannabis as a whole product. Despite disappointing sales at the end of 2007, the Minister of Health, Welfare and Sport has announced that the current policy will be extended for a further five years. The Minister also indicated that he would consider discontinuing the availability of medicinal cannabis for patients, if new cannabis products are granted market authorization. This might, however, give rise to a new era of illegal cannabis use for medicinal purposes, notably for the use as a whole product.

Sensitization and allergy to Cannabis sativa leaves in a population of tomato (Lycopersicon esculentum)-sensitized patients.

PubMed

de Larramendi, Carlos Hernando; Carnés, Jerónimo; García-Abujeta, José Luís; García-Endrino, Ana; Muñoz-Palomino, Elena; Huertas, Angel Julio; Fernández-Caldas, Enrique; Ferrer, Angel

2008-01-01

Cases of allergy to Cannabis sativa have occasionally been reported, but both the allergenic profile and eventual cross-reactivity pattern remain unknown. To analyze the allergenic profile of a population of patients from Spain sensitized to C. sativa and to characterize the C. sativa leaf extract. A total of 32 subjects were enrolled in the study: group A, 10 individuals sensitized to tomato, reporting reactions by contact or inhalation to Cannabis; group B, 14 individuals sensitized to tomato, without reactions to Cannabis; group C, 8 individuals not sensitized to tomato and without reactions to Cannabis. Sensitivity to Cannabis, tomato and peach peel, Platanus hybrida and Artemisia vulgaris pollen extracts was measured by skin tests and specific IgE. Individual immunoblots and inhibition experiments with a pool of sera were conducted. All tomato-sensitized subjects (and 1 negative) had positive skin tests to C. sativa leaves and hashish. Specific IgE to C. sativa and peach peel was more common than to tomato. Immunoblot experiments showed 2 prominent bands of 10 and 14 kDa and 2 weakly recognized bands of 30 and 45 kDa. Tomato, peach and A. vulgaris extracts inhibited most of the bands present in C. sativa. P. hybrida inhibited only the high-molecular-weight bands. Sensitization to C. sativa with or without symptoms is frequent among patients in Spain sensitized to tomato. C. sativa leaves are a potential allergenic source and their allergens may cross-react with other allergenic sources from plants (fruit peels and pollen). (c) 2008 S. Karger AG, Basel

Antecedents and consequences of cannabis use among racially diverse cannabis users: an analysis from Ecological Momentary Assessment.

PubMed

Buckner, Julia D; Zvolensky, Michael J; Crosby, Ross D; Wonderlich, Stephen A; Ecker, Anthony H; Richter, Ashley

2015-02-01

Cannabis remains the most commonly used illicit substance and use rates are rising. Notably, the prevalence of cannabis use disorders (CUD) nearly equals that of other illicit substance use disorders combined. Thus, the present study aimed to identify cognitive, affective, and situational predictors and consequences of ad-lib cannabis use in a racially diverse sample. The sample consisted of 93 current cannabis users (34.4% female; 57.1% non-Hispanic Caucasian), 87.1% of whom evinced a current CUD. Ecological Momentary Assessment was used to collect frequent ratings of cannabis withdrawal, craving, affect, cannabis use motives, and peer cannabis use over two weeks. Mixed effects linear models examined within- and between-day correlates and consequences of cannabis use. Withdrawal and craving were higher on cannabis use days than non-use days. Withdrawal, craving, and positive and negative affect were higher immediately prior to cannabis use compared to non-use episodes. Withdrawal and craving were higher among those who subsequently used cannabis than those who did not. Cannabis use resulted in less subsequent withdrawal, craving, and negative affect. Enhancement and coping motives were the most common reasons cited for use. Withdrawal and negative affect were related to using cannabis for coping motives and social motives. Participants were most likely to use cannabis if others were using, and withdrawal and craving were greater in social situations when others were using. Data support the contention that cannabis withdrawal and craving and affect and peer use play important roles in the maintenance of cannabis use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Psychiatric effects of cannabis use.

PubMed

Tunving, K

1985-09-01

That cannabis use may provoke mental disturbances is well known to Scandinavian psychiatrists today. A review of the psychiatric aspects of cannabis use is given, and the clinical signs of 70 cases of cannabis psychoses collected in Sweden are described. The bluntness and "amotivation" following chronic cannabis use are discussed. Anxiety reactions, flashbacks, dysphoric reactions and an abstinence syndrome are all sequels of cannabis use. Three risk groups begin to emerge: a) Young teenage cannabis users who lose some of their capacity to learn complex functions and who flee from reality to a world of dreams. With its sedative effect, cannabis could modify such emotions as anger and anxiety and slow down the liberation process of adolescence. b) Heavy daily users, often persons who cannot cope with depression or their life circumstances. c) Psychiatric patients whose resistance to relapses into psychotic reactions might be diminished according to the psychotropic effects of cannabis.

History of cannabis and its preparations in saga, science, and sobriquet.

PubMed

Russo, Ethan B

2007-08-01

Cannabis sativa L. is possibly one of the oldest plants cultivated by man, but has remained a source of controversy throughout its history. Whether pariah or panacea, this most versatile botanical has provided a mirror to medicine and has pointed the way in the last two decades toward a host of medical challenges from analgesia to weight loss through the discovery of its myriad biochemical attributes and the endocannabinoid system wherein many of its components operate. This study surveys the history of cannabis, its genetics and preparations. A review of cannabis usage in Ancient Egypt will serve as an archetype, while examining first mentions from various Old World cultures and their pertinence for contemporary scientific investigation. Cannabis historians of the past have provided promising clues to potential treatments for a wide array of currently puzzling medical syndromes including chronic pain, spasticity, cancer, seizure disorders, nausea, anorexia, and infectious disease that remain challenges for 21st century medicine. Information gleaned from the history of cannabis administration in its various forms may provide useful points of departure for research into novel delivery techniques and standardization of cannabis-based medicines that will allow their prescription for treatment of these intractable medical conditions.

Cannabis Effects on Driving Skills

PubMed Central

Hartman, Rebecca L.; Huestis, Marilyn A.

2013-01-01

BACKGROUND Cannabis is the most prevalent illicit drug identified in impaired drivers. The effects of cannabis on driving continue to be debated, making prosecution and legislation difficult. Historically, delays in sample collection, evaluating the inactive Δ9-tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-THC, and polydrug use have complicated epidemiologic evaluations of driver impairment after cannabis use. CONTENT We review and evaluate the current literature on cannabis’ effects on driving, highlighting the epidemiologic and experimental data. Epidemiologic data show that the risk of involvement in a motor vehicle accident (MVA) increases approximately 2-fold after cannabis smoking. The adjusted risk of driver culpability also increases substantially, particularly with increased blood THC concentrations. Studies that have used urine as the biological matrix have not shown an association between cannabis and crash risk. Experimental data show that drivers attempt to compensate by driving more slowly after smoking cannabis, but control deteriorates with increasing task complexity. Cannabis smoking increases lane weaving and impaired cognitive function. Critical-tracking tests, reaction times, divided-attention tasks, and lane-position variability all show cannabis-induced impairment. Despite purported tolerance in frequent smokers, complex tasks still show impairment. Combining cannabis with alcohol enhances impairment, especially lane weaving. SUMMARY Differences in study designs frequently account for inconsistencies in results between studies. Participant-selection bias and confounding factors attenuate ostensible cannabis effects, but the association with MVA often retains significance. Evidence suggests recent smoking and/or blood THC concentrations 2–5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Future cannabis-and-driving research should emphasize challenging tasks, such as divided attention

Cannabis Use Disorder in Adolescence.

PubMed

Simpson, Annabelle K; Magid, Viktoriya

2016-07-01

Cannabis use in the adolescent population poses a significant threat of addiction potential resulting in altered neurodevelopment. There are multiple mechanisms of treatment of cannabis use disorder including behavioral therapy management and emerging data on treatment via pharmacotherapy. Recognizing the diagnostic criteria for cannabis use disorder, cannabis withdrawal syndrome, and mitigating factors that influence adolescent engagement in cannabis use allows for comprehensive assessment and management in the adolescent population. Copyright © 2016 Elsevier Inc. All rights reserved.

Multidimensional analysis of cannabis volatile constituents: identification of 5,5-dimethyl-1-vinylbicyclo[2.1.1]hexane as a volatile marker of hashish, the resin of Cannabis sativa L.

PubMed

Marchini, Marie; Charvoz, Céline; Dujourdy, Laurence; Baldovini, Nicolas; Filippi, Jean-Jacques

2014-11-28

The volatile constituents of drug samples derived from Cannabis sativa L. were investigated by means of headspace solid phase microextraction (HS-SPME) and gas chromatography techniques (GC-MS, GC×GC-MS). Samples of cannabis herb and hashish showed clear differences in their volatile chemical profiles, mostly resulting from photo-oxidation processes occurring during the transformation of fresh cannabis herb into hashish. Most unexpectedly, we could demonstrate hashish samples as containing remarkable amounts of a rare and unusual monoterpene - 5,5-dimethyl-1-vinylbicyclo[2.1.1]hexane - among the volatile compounds detected in their headspaces. We gave evidence for the formation of this compound from the light induced rearrangement of β-myrcene during the manufacture of hashish. In view of its high abundance among volatile constituents of cannabis resin and its scarce occurrence in other natural volatile extracts, we propose to rename this specific monoterpene hashishene. Copyright © 2014 Elsevier B.V. All rights reserved.

Perceived barriers for cannabis cessation: Relations to cannabis use problems, withdrawal symptoms, and self-efficacy for quitting.

PubMed

Zvolensky, Michael J; Paulus, Daniel J; Garey, Lorra; Manning, Kara; Hogan, Julianna B D; Buckner, Julia D; Rogers, Andrew H; Kathryn McHugh, R

2018-01-01

Cannabis is the most widely used illicit substance in the United States. Regular cannabis use appears to be a dynamic, chronic process consisting of multiple quit attempts, periods of reduction, periods of abstinence, and periods of continual use. Cannabis-related processes, including withdrawal, problematic consequences of use, and self-efficacy for quitting each contribute to the cycle of use and, in part, are maintained and reinforced by perceived barriers for cannabis cessation. Yet, no work has examined the association between perceived barriers for cannabis cessation and clinically-relevant processes related to cannabis use. To address this gap, the current study recruited a racially diverse sample (N=145, 63.4% Black or African American) of cannabis users from the community to test the hypothesis that greater perceived barriers for quitting cannabis was related to more cannabis use problems, more cannabis withdrawal symptoms, and lower self-efficacy for quitting cannabis. Structural equation modeling suggested that greater perceived barriers for quitting cannabis was uniquely associated with cannabis use problems (β=0.50, 95%CI [0.39, 0.65], p<0.001), greater withdrawal symptoms (β=0.39, 95%CI [0.30, 0.50], p<0.001), and lower self-efficacy for quitting (β=-0.17, 95%CI [-0.21, -0.02], p=0.028). The results of this study indicate perceived barriers for cannabis cessation may help in better understanding an array of clinically significant cannabis use processes. Indeed, the observed pattern of findings add to current theoretical models of substance use that aim to identify unique risk processes that may maintain substance use and provide valuable information that can be used to inform treatment for cannabis users. Published by Elsevier Ltd.

Preparation and Distribution of Cannabis and Cannabis-Derived Dosage Formulations for Investigational and Therapeutic Use in the United States

PubMed Central

Thomas, Brian F.; Pollard, Gerald T.

2016-01-01

Cannabis is classified as a schedule I controlled substance by the US Drug Enforcement Agency, meaning that it has no medicinal value. Production is legally restricted to a single supplier at the University of Mississippi, and distribution to researchers is tightly controlled. However, a majority of the population is estimated to believe that cannabis has legitimate medical or recreational value, numerous states have legalized or decriminalized possession to some degree, and the federal government does not strictly enforce its law and is considering rescheduling. The explosive increase in open sale and use of herbal cannabis and its products has occurred with widely variable and in many cases grossly inadequate quality control at all levels—growing, processing, storage, distribution, and use. This paper discusses elements of the analytical and regulatory system that need to be put in place to ensure standardization for the researcher and to reduce the hazards of contamination, overdosing, and underdosing for the end-user. PMID:27630566

Analysis of Cannabis Seizures in NSW, Australia: Cannabis Potency and Cannabinoid Profile

PubMed Central

Li, Kong M.; Arnold, Jonathon C.; McGregor, Iain S.

2013-01-01

Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ9-tetrahydrocannabinol (THC) and low levels of other phytocannabinoids, particularly cannabidiol (CBD). Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales “Cannabis Cautioning” scheme. A further 26 “Known Provenance” samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG), and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC), cannabinol (CBN) and tetrahydrocannabivarin (THC-V). The “Cannabis Cautioning” samples showed high mean THC content (THC+THC-A = 14.88%) and low mean CBD content (CBD+CBD-A = 0.14%). A modest level of CBG was detected (CBG+CBG-A = 1.18%) and very low levels of CBC, CBN and THC-V (<0.1%). “Known Provenance” samples showed no significant differences in THC content between those seized from indoor versus outdoor cultivation sites. The present analysis echoes trends reported in other countries towards the use of high potency cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed. PMID:23894589

Analysis of cannabis seizures in NSW, Australia: cannabis potency and cannabinoid profile.

PubMed

Swift, Wendy; Wong, Alex; Li, Kong M; Arnold, Jonathon C; McGregor, Iain S

2013-01-01

Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ(9)-tetrahydrocannabinol (THC) and low levels of other phytocannabinoids, particularly cannabidiol (CBD). Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales "Cannabis Cautioning" scheme. A further 26 "Known Provenance" samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG), and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC), cannabinol (CBN) and tetrahydrocannabivarin (THC-V). The "Cannabis Cautioning" samples showed high mean THC content (THC+THC-A = 14.88%) and low mean CBD content (CBD+CBD-A = 0.14%). A modest level of CBG was detected (CBG+CBG-A = 1.18%) and very low levels of CBC, CBN and THC-V (<0.1%). "Known Provenance" samples showed no significant differences in THC content between those seized from indoor versus outdoor cultivation sites. The present analysis echoes trends reported in other countries towards the use of high potency cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed.

The Interactive Influence of Cannabis-Related Negative Expectancies and Coping Motives on Cannabis Use Behavior and Problems.

PubMed

Foster, Dawn W; Jeffries, Emily R; Zvolensky, Michael J; Buckner, Julia D

2016-09-18

The present study tested whether coping motives for cannabis use moderate the effect of negative expectancies on cannabis use. Participants were 149 (36.2% female, 61.59% non-Hispanic Caucasian) current cannabis users aged 18-36 (M = 21.01, SD = 3.09) who completed measures of cannabis-related expectancies and motives for use. Hierarchical multiple regressions were employed to investigate the predictive value of the interaction between negative expectancies and coping motives on cannabis use outcomes. Results revealed interactions between negative expectancies and coping motives with respect to past 90 day cannabis use frequency and cannabis problems. Global negative effects expectancies were associated with less frequent cannabis use, particularly among those with fewer coping motives. However, negative expectancies were related to more cannabis problems, particularly among those with higher coping motives. These results suggest it may be advisable to take coping motives into account when addressing expectancies among cannabis users.

[Cannabis and mood].

PubMed

Sanches, Rafael Faria; Marques, João Mazzoncini de Azevedo

2010-06-01

Evaluate the relationship between acute and chronic use of cannabis and mood changes. Articles were selected by electronic search in PubMed. Chapters in books and reference lists of selected articles were also reviewed. As the research did not involve humans, there was no evaluation by a Research Ethics Committee. High rates of comorbidity between use/abuse/dependence of cannabis and affective disorders in longitudinal studies and in clinical samples were observed. Longitudinal studies indicate that, in long-term, the higher use of cannabis is associated with an increased risk of developing bipolar disorder, and probably, major depression in subjects initially without affective disorder, but was not found increased risk of cannabis use among those initially only with mania or depression. Another important observation is that substance abuse in bipolar patients may be associated with a number of negative characteristics, such as difficulty in recovering the affective symptoms, more hospitalizations, poor compliance with treatment, increased risk of suicide, aggression and a poor response to lithium. Psychosocial and pharmacological treatments are indicated for the management of comorbidity between cannabis and affective disorders. The relationship between cannabis use and mood changes are observed both in the epidemiological research and in the clinical settings.

Cannabis and sport.

PubMed

Saugy, M; Avois, L; Saudan, C; Robinson, N; Giroud, C; Mangin, P; Dvorak, J

2006-07-01

Cannabis is on the list of prohibited substances in the practice of sport, although its performance enhancing effect has not yet been proved. Its popularity among the younger generations as a social drug puts cannabis at the top of the list of compounds detected by the anti-doping laboratories accredited by the World Anti-Doping Agency worldwide. The management of the results of urine analysis is quite difficult for the medical and disciplinary committees not only because of the social use of the substance, but also because of the interpretation of the analytical data from urine samples. This paper gives an overview of what is presently known about cannabis in relation with the practice of sport. Review of literature on the cannabis and exercise, its effect in the body, and the problems with interpretation of results when it is detected in urine. The paper outlines the major effects of cannabis in the context of its social use and its use for sport activities. The difficulties in the interpretation of urine sample analysis results because of the protracted excretion time of the main metabolite, long after the intake, are described. There is an urgent need for sport authorities to take measures necessary to avoid players misusing cannabis.

Using cannabis to help you sleep: heightened frequency of medical cannabis use among those with PTSD.

PubMed

Bonn-Miller, Marcel O; Babson, Kimberly A; Vandrey, Ryan

2014-03-01

The use of cannabis for medical purposes is proliferating in the U.S., and PTSD is an explicitly approved condition for accessing medical cannabis in 5 states. Prior research suggests that people with PTSD often use cannabis to help cope with their condition, and that doing so results in more frequent and problematic cannabis use patterns. Specific coping motivations, such as sleep improvement, among medical cannabis users, have not been examined. The present study evaluated specific coping use motivations, frequency of cannabis and alcohol use, and mental health among a convenience sample of patients (N=170) at a medical cannabis dispensary in California. Those with high PTSD scores were more likely to use cannabis to improve sleep, and for coping reasons more generally, compared with those with low PTSD scores. Cannabis use frequency was greater among those with high PTSD scores who used for sleep promoting purposes compared with those with low PTSD scores or those who did not use for sleep promoting purposes. Consistent with prior research, this study found increased rates of coping-oriented use of cannabis and greater frequency of cannabis use among medical users with high PTSD scores compared with low PTSD scores. In addition, sleep improvement appears to be a primary motivator for coping-oriented use. Additional research is needed to examine the health consequences of this pattern of cannabis use and whether alternative sleep promoting interventions (e.g. CBT-I) could reduce the reliance on cannabis for adequate sleep among those with PTSD. Published by Elsevier Ireland Ltd.

Are early-onset cannabis smokers at an increased risk of depression spells?

PubMed

Fairman, Brian J; Anthony, James C

2012-04-01

A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005-2009 (74-76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR=1.7 and 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another. Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to diminish the cannabis-associated risk. Copyright © 2011

Are early-onset cannabis smokers at an increased risk of depression spells?

PubMed Central

Fairman, Brian J.; Anthony, James C.

2012-01-01

Background A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). Methods The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005–2009 (74–76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. Results About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR = 1.7 & 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another. Limitations Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. Conclusion Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to

Cognitive functioning of long-term heavy cannabis users seeking treatment.

PubMed

Solowij, Nadia; Stephens, Robert S; Roffman, Roger A; Babor, Thomas; Kadden, Ronald; Miller, Michael; Christiansen, Kenneth; McRee, Bonnie; Vendetti, Janice

2002-03-06

Cognitive impairments are associated with long-term cannabis use, but the parameters of use that contribute to impairments and the nature and endurance of cognitive dysfunction remain uncertain. To examine the effects of duration of cannabis use on specific areas of cognitive functioning among users seeking treatment for cannabis dependence. Multisite retrospective cross-sectional neuropsychological study conducted in the United States (Seattle, Wash; Farmington, Conn; and Miami, Fla) between 1997 and 2000 among 102 near-daily cannabis users (51 long-term users: mean, 23.9 years of use; 51 shorter-term users: mean, 10.2 years of use) compared with 33 nonuser controls. Measures from 9 standard neuropsychological tests that assessed attention, memory, and executive functioning, and were administered prior to entry to a treatment program and following a median 17-hour abstinence. Long-term cannabis users performed significantly less well than shorter-term users and controls on tests of memory and attention. On the Rey Auditory Verbal Learning Test, long-term users recalled significantly fewer words than either shorter-term users (P =.001) or controls (P =.005); there was no difference between shorter-term users and controls. Long-term users showed impaired learning (P =.007), retention (P =.003), and retrieval (P =.002) compared with controls. Both user groups performed poorly on a time estimation task (P<.001 vs controls). Performance measures often correlated significantly with the duration of cannabis use, being worse with increasing years of use, but were unrelated to withdrawal symptoms and persisted after controlling for recent cannabis use and other drug use. These results confirm that long-term heavy cannabis users show impairments in memory and attention that endure beyond the period of intoxication and worsen with increasing years of regular cannabis use.

Chronic effects of cannabis use on the auditory mismatch negativity.

PubMed

Greenwood, Lisa-Marie; Broyd, Samantha J; Croft, Rodney; Todd, Juanita; Michie, Patricia T; Johnstone, Stuart; Murray, Robin; Solowij, Nadia

2014-03-15

Cannabis use is associated with the development of psychotic symptoms and increased risk for schizophrenia. The mismatch negativity (MMN) is a brain event-related potential marker of change detection thought to index glutamatergic N-methyl-D-aspartate receptor-mediated neurotransmission, which is known to be deficient in schizophrenia. This study examined auditory MMN in otherwise healthy chronic cannabis users compared with nonuser control subjects. Forty-two chronic cannabis users and 44 nonuser healthy control subjects completed a multi-feature MMN paradigm, which included duration, frequency, and intensity deviants (deviants 6%; standards 82%). The MMN was compared between users and control subjects as well as between long- and short-term users and age- and gender-matched control subjects. Associations between MMN, cannabis use measures, and symptoms were examined. The MMN amplitude was significantly reduced to frequency but not duration or intensity deviants in overall cannabis users relative to control subjects. Frequency MMN was similarly attenuated in short- and long-term users relative to control subjects. Long-term users also exhibited reduced duration MMN relative to control subjects and short-term users and this was correlated with increased duration of exposure to cannabis and increased psychotic-like experiences during intoxication. In short-term users, a younger age of onset of regular cannabis use and greater frequency of use were associated with greater psychotic-like experiences and symptomatic distress. These results suggest impaired sensory memory that might reflect N-methyl-D-aspartate receptor dysfunction in chronic cannabis users. The pattern of MMN alterations in cannabis users differed from that typically observed in patients with schizophrenia, indicating overlapping but distinct underlying pathology. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Prior Cannabis Use Is Associated with Outcome after Intracerebral Hemorrhage.

PubMed

Di Napoli, Mario; Zha, Alicia M; Godoy, Daniel A; Masotti, Luca; Schreuder, Floris H B M; Popa-Wagner, Aurel; Behrouz, Réza

2016-01-01

Recent evidence suggests that a potential harmful relationship exists between cannabis use and ischemic stroke. The purpose of this study was to determine the implications of cannabis use in intracerebral hemorrhage (ICH) patients. An analysis of an international, multicenter, observational database of consecutive patients with spontaneous ICH was conducted. We extracted the following characteristics on presentation: demographics, risk factors, antiplatelet or anticoagulant use, Glasgow Coma Scale, ICH score, neuroimaging parameters, and urine toxicology screen (UTS) results. Modified Rankin Scale (mRS) score was utilized for determination of outcome at discharge. Adjusted logistic ordinal regression was used as shift analysis to assess the impact of cannabis use on mRS score at discharge. The adjusted common OR measured the likelihood that cannabis use would lead to lower mRS scores. Within a cohort of 725 spontaneous ICH patients, UTS was positive for cannabinoids in 8.6%. Cannabinoids-positive (CB+) patients were more frequently Caucasian (p < 0.001), younger (p < 0.001), and had lower median ICH scores on admission (p = 0.017) than those who were cannabinoids-negative. CB+ patients also showed a shift toward better outcome in the distribution of mRS categories, with an adjusted common OR of 0.544 (95% CI 0.330-0.895, p = 0.017). In this multinational cohort, cannabis use was discovered in nearly 10% of patients with spontaneous ICH. Although there was no relationship between cannabis use and specific ICH characteristics, CB+ patients had milder ICH presentation and less disability at discharge. © 2016 S. Karger AG, Basel.

Cannabis Users' Recommended Warnings for Packages of Legally Sold Cannabis: An Australia-Centered Study.

PubMed

Malouff, John M; Johnson, Caitlin E; Rooke, Sally E

2016-01-01

Introduction: Although cannabis use creates health risks, governments have recently been legalizing either medical use or leisure use. These governments can mandate health warnings on cannabis packages. Prior research examined recommended warnings of cannabis experts. The aim of this study was to obtain suggested cannabis health and safety warnings from cannabis users. Methods: We used a media release, Facebook postings, and announcements in university classes to seek individuals who had used cannabis at least once according to their own report. Using online data collection software that keeps participants anonymous, we asked the individuals to suggest a warning that governments could mandate on cannabis packages. Results: In total, 288 users suggested warnings. Categorizing the warnings into content categories led to six warning topics: (1) risk of harm to mental health and psychological functioning; (2) risk of operating machinery while under the influence; (3) short-term physical side effects; (4) responsible use; (5) long-term negative physical effects; and (6) dependence, addiction, or abuse. The user-suggested warnings overlapped with six expert-recommended warnings identified in prior survey research and included two content areas that did not feature in expert-recommended warnings: short-term physical side effects and the importance of responsible use. Conclusions: The results are consistent with prior findings that some youths perceive cannabis use as potentially harmful. The current findings provide possible new content for warnings on cannabis packages.

Cannabis and schizophrenia.

PubMed

Pushpa-Rajah, Jonathan A; McLoughlin, Benjamin C; Gillies, Donna; Rathbone, John; Variend, Hannele; Kalakouti, Eliana; Kyprianou, Katerina

2015-03-01

Many people with schizophrenia smoke cannabis, and it is unclear why a large proportion do so and if the effects are harmful or beneficial. It is also unclear what the best method is to allow people with schizophrenia to alter their cannabis intake. To assess the effects of specific psychological treatments for cannabis reduction in people with schizophrenia. To assess the effects of antipsychotics for cannabis reduction in people with schizophrenia. To assess the effects of cannabinoids (cannabis-related chemical compounds derived from cannabis or manufactured) for symptom reduction in people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (August 2013) and all references of articles selected for further relevant trials. We contacted the first author of included studies for unpublished trials or data. We included all randomized controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed: (1) treatments to reduce cannabis use in people with schizophrenia and (2) the effects of cannabinoids on people with schizophrenia. Results are limited and inconclusive due to the small number and size of randomized controlled trials available and quality of data reporting within these trials. Currently, there is no evidence to demonstrate that one type of adjunct psychological therapy or one type of drug therapy is more effective than another. There is also insufficient evidence to show that cannabidiol has an antipsychotic effect. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[Cannabis--abuse and consequences].

PubMed

Wøien, Vidar-André; Horwitz, Henrik; Høgberg, Lotte C G; Askaa, Bjarke; Jürgens, Gesche

2015-02-02

Cannabis is the world's most popular illicit drug, and around half of all Danes have tried it at least once. In this paper we review the pharmacodynamic and pharmacokinetic properties of cannabis. We also discuss the treatment of cannabis intoxication and present data from The Danish Poison Information Center.

Adherence to Medical Cannabis Among Licensed Patients in Israel

PubMed Central

Zolotov, Yuval; Baruch, Yehuda; Reuveni, Haim; Magnezi, Racheli

2016-01-01

Abstract Objectives: To evaluate adherence among Israeli patients who are licensed to use medical cannabis and to identify factors associated with adherence to medical cannabis. Methods: Ninety-five novice licensed patients were interviewed for this cross-sectional study. The questionnaire measured demographics, the perceived patient–physician relationship, and the level of patients' active involvement in their healthcare. In addition, patients were queried about adverse effect(s) and about their overall satisfaction from this medical treatment. Results: Eighty percent (n=76) has been identified as adherent to medical cannabis use. Variables found associated with adherence were “country of origin” (immigrant status), “type of illness” (cancer vs. non-cancer), and “experiencing adverse effect(s).” Three predictors of adherence were found significant in a logistic regression model: “type of illness” (odds ratio [OR] 0.101), patient–physician relationship (OR 1.406), and level of patient activation (OR 1.132). 71.5% rated themselves being “completely satisfied” or “satisfied” from medical cannabis use. Conclusions: Our findings show a relatively high adherence rate for medical cannabis, as well as relative safety and high satisfaction among licensed patients. Additionally indicated is the need to develop and implement standardized education about this evolving field—to both patients and physicians. PMID:28861475

Adherence to Medical Cannabis Among Licensed Patients in Israel.

PubMed

Zolotov, Yuval; Baruch, Yehuda; Reuveni, Haim; Magnezi, Racheli

2016-01-01

Objectives: To evaluate adherence among Israeli patients who are licensed to use medical cannabis and to identify factors associated with adherence to medical cannabis. Methods: Ninety-five novice licensed patients were interviewed for this cross-sectional study. The questionnaire measured demographics, the perceived patient-physician relationship, and the level of patients' active involvement in their healthcare. In addition, patients were queried about adverse effect(s) and about their overall satisfaction from this medical treatment. Results: Eighty percent ( n =76) has been identified as adherent to medical cannabis use. Variables found associated with adherence were "country of origin" (immigrant status), "type of illness" (cancer vs. non-cancer), and "experiencing adverse effect(s)." Three predictors of adherence were found significant in a logistic regression model: "type of illness" (odds ratio [OR] 0.101), patient-physician relationship (OR 1.406), and level of patient activation (OR 1.132). 71.5% rated themselves being "completely satisfied" or "satisfied" from medical cannabis use. Conclusions: Our findings show a relatively high adherence rate for medical cannabis, as well as relative safety and high satisfaction among licensed patients. Additionally indicated is the need to develop and implement standardized education about this evolving field-to both patients and physicians.

Cannabis Mobile Apps: A Content Analysis.

PubMed

Ramo, Danielle E; Popova, Lucy; Grana, Rachel; Zhao, Shirley; Chavez, Kathryn

2015-08-12

Mobile technology is pervasive and widely used to obtain information about drugs such as cannabis, especially in a climate of rapidly changing cannabis policy; yet the content of available cannabis apps is largely unknown. Understanding the resources available to those searching for cannabis apps will clarify how this technology is being used to reflect and influence cannabis use behavior. We investigated the content of 59 cannabis-related mobile apps for Apple and Android devices as of November 26, 2014. The Apple and Google Play app stores were searched using the terms "cannabis" and "marijuana." Three trained coders classified the top 20 apps for each term and each store, using a coding guide. Apps were examined for the presence of 20 content codes derived by the researchers. Total apps available for each search term were 124 for cannabis and 218 for marijuana in the Apple App Store, and 250 each for cannabis and marijuana on Google Play. The top 20 apps in each category in each store were coded for 59 independent apps (30 Apple, 29 Google Play). The three most common content areas were cannabis strain classification (33.9%), facts about cannabis (20.3%), and games (20.3%). In the Apple App Store, most apps were free (77%), all were rated "17+" years, and the average user rating was 3.9/5 stars. The most popular apps provided cannabis strain classifications (50%), dispensary information (27%), or general facts about cannabis (27%). Only one app (3%) provided information or resources related to cannabis abuse, addiction, or treatment. On Google Play, most apps were free (93%), rated "high maturity" (79%), and the average user rating was 4.1/5. The most popular app types offered games (28%), phone utilities (eg, wallpaper, clock; 21%) and cannabis food recipes (21%); no apps addressed abuse, addiction, or treatment. Cannabis apps are generally free and highly rated. Apps were most often informational (facts, strain classification), or recreational (games), likely

[Cannabis-induced disorders].

PubMed

Soyka, M; Preuss, U; Hoch, E

2017-03-01

Use and misuse of cannabis and marihuana are frequent. About 5% of the adult population are current users but only 1.2% are dependent. The medical use of cannabis is controversial but there is some evidence for improvement of chronic pain and spasticity. The somatic toxicity of cannabis is well proven but limited and psychiatric disorders induced by cannabis are of more relevance, e.g. cognitive disorders, amotivational syndrome, psychoses and delusional disorders as well as physical and psychological dependence. The withdrawal symptoms are usually mild and do not require pharmacological interventions. To date there is no established pharmacotherapy for relapse prevention. Psychosocial interventions include psychoeducation, behavioral therapy and motivational enhancement. The CANDIS protocol is the best established German intervention among abstinence-oriented therapies.

The Canadian Cannabis Act legalizes and regulates recreational cannabis use in 2018.

PubMed

Cox, Chelsea

2018-03-01

Canada is on the cusp of an unprecedented change in its governmental approach to recreational cannabis consumption. By July of 2018 the country will legalize and regulate recreational cannabis use across the country via the implementation of the Cannabis Act, representing the second country in the world and the first in North America to do so. With almost half of Canadians having admitted to using the drug illegally, this change in policy has been long advocated. While medical cannabis has been legal since 2001 this represents the first time in recent history that recreational cannabis will be legal on a federal level. As the country moves away from criminal prohibition into a framework centered on harm minimization and public health and safety, the policy specifics are being worked out by a variety of stakeholders. With limited peer-reviewed research and similar regulatory schemes to shape the Cannabis Act off of, Canada is entering unchartered territory. As other countries around the world struggle with illegal cannabis consumption, the Canadian example and novel regulatory scheme could prove a useful guiding tool for future policy in other jurisdictions. The following paper discusses key areas to watch and a brief intro of how Canada got to where it is and the foundational need for a shift in policy. Copyright © 2018 Elsevier B.V. All rights reserved.

Cross-sectional and prospective relation of cannabis potency, dosing and smoking behaviour with cannabis dependence: an ecological study.

PubMed

van der Pol, Peggy; Liebregts, Nienke; Brunt, Tibor; van Amsterdam, Jan; de Graaf, Ron; Korf, Dirk J; van den Brink, Wim; van Laar, Margriet

2014-07-01

Increased delta-9-tetrahydrocannabinol (THC) concentrations in cannabis may lead to higher THC exposure, cannabis dependence and treatment need, but users may also adapt the actual intake of THC through reduced inhalation of THC containing smoke (titration). We investigated whether consumers of stronger cannabis use less cannabis per joint or inhale less smoke than those using less potent cannabis and whether these factors predict cannabis dependence severity. Heavy cannabis users (n = 98) brought their own cannabis, rolled a joint and smoked it ad libitum in a naturalistic setting. We analysed the content of the joint, its association with smoking behaviour and the cross-sectional and prospective (1.5-year follow-up) relations between smoking behaviour and cannabis dependence severity (total number of DSM-IV dependence symptoms). THC concentration in cannabis (range 1.10-24.70%) was correlated positively with cannabis dose per joint (b = 0.008, P = 0.01), but the resulting THC concentration per joint (range 0.24-15.72%) was associated negatively with inhalation volume (b = -0.05, P = 0.03). Smoking behaviour measures (number of puffs, inhaled volume, reduction of puff volume and puff duration while smoking) predicted follow-up dependence severity, independently of baseline dependence severity and monthly THC dose (number of joints × cannabis dose × cannabis THC concentration). Monthly THC dose only predicted follow-up dependence severity when unadjusted for baseline severity. Cannabis users titrate their delta-9-tetrahydrocannabinol intake by inhaling lower volumes of smoke when smoking strong joints, but this does not fully compensate for the higher cannabis doses per joint when using strong cannabis. Thus, users of more potent cannabis are generally exposed to more delta-9-tetrahydrocannabinol. Smoking behaviour appears to be a stronger predictor for cannabis dependence severity than monthly delta-9-tetrahydrocannabinol dose. �

Detection of in utero cannabis exposure by umbilical cord analysis.

PubMed

Kim, Jiyoung; de Castro, Ana; Lendoiro, Elena; Cruz-Landeira, Angelines; López-Rivadulla, Manuel; Concheiro, Marta

2018-04-01

According to the 2014 National Survey on Drug Use and Health, 5.3% of pregnant women smoked marijuana in the past month. This prevalence is expected to increase as a growing number of states and countries are now considering legalization. Although the umbilical cord is becoming a useful objective tool to detect in utero drug exposure, currently data about analytical methods and its utility to detect cannabis exposure are scarce. The objective of this work was to develop a method for the determination of Δ 9 -tetrahydrocannabinol (THC), 11-hydroxyTHC (THC-OH), 11-nor-9-carboxy-THC (THCCOOH), 8-β-11-dihydroxyTHC (THC-diOH), THC and THCCOOH glucuronides, and cannabidiol (CBD) in the umbilical cord by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with dual ionization source. Umbilical cord samples (0.5 g) were homogenized in methanol and extracted by solid-phase extraction. Reversed-phase chromatographic separation was performed in 14 minutes, and 2 transitions per analyte were monitored in multiple reaction monitoring mode. Method validation included linearity (1-10 to 20-200 ng/g), precision (4.1%-23.4%), accuracy (87.5%-111.4%), matrix effect (-54.8% to -5.8%), extraction efficiency (25%-45.6%), limits of detection and quantification (1-10 ng/g), and endogenous (n = 5) or exogenous interferences (not detected). The method was applied to 13 authentic samples from cannabis-exposed newborns, which meconium samples had tested positive for cannabis. Twelve cord specimens tested positive for THCCOOH-glucuronide (1.6-19.1 ng/g). We developed and validated a specific and sensitive method for the simultaneous determination of THC, its metabolites, including THC and THCCOOH glucuronides, and CBD in umbilical cord samples by LC-MS/MS. The analysis of authentic samples showed the usefulness of umbilical cord to detect cannabis in utero exposure. Copyright © 2017 John Wiley & Sons, Ltd.

Cannabis arteritis: review of the literature.

PubMed

Cottencin, Olivier; Karila, Laurent; Lambert, Marc; Arveiller, Catherine; Benyamina, Amine; Boissonas, Alain; Goudemand, Michel; Reynaud, Michel

2010-12-01

Consumption of cannabis in young adults has continued to increase in recent years. Cannabis arteritis was first described in the 1960s, but the number of cases has continued to increase. We reviewed current knowledge of the different types of cannabis arteritis in young adults and found 70 cases of cannabis arteritis in the literature. We discuss physiopathological arguments in favor of cannabis vascular toxicity per se, although we did not find sufficient evidence to identify cannabis arteritis as a specific diagnostic entity. Many factors suggest a link between cannabis consumption and arteritis in young adults, but it is difficult to say whether this type of arteritis is similar to thromboangiitis obliterans. We were unable to demonstrate a formal association between cannabis smoking and the development of thromboangiitis obliterans, because most case reports showed associated tobacco smoking (97%) and the number of years cannabis had been smoked by the participants was mostly unknown. Cannabis consumption would however seems to be an aggravating factor, together with tobacco, in arteritis, which occurs in young adults.

Cannabis Users' Recommended Warnings for Packages of Legally Sold Cannabis: An Australia-Centered Study

PubMed Central

Malouff, John M.; Johnson, Caitlin E.; Rooke, Sally E.

2016-01-01

Abstract Introduction: Although cannabis use creates health risks, governments have recently been legalizing either medical use or leisure use. These governments can mandate health warnings on cannabis packages. Prior research examined recommended warnings of cannabis experts. The aim of this study was to obtain suggested cannabis health and safety warnings from cannabis users. Methods: We used a media release, Facebook postings, and announcements in university classes to seek individuals who had used cannabis at least once according to their own report. Using online data collection software that keeps participants anonymous, we asked the individuals to suggest a warning that governments could mandate on cannabis packages. Results: In total, 288 users suggested warnings. Categorizing the warnings into content categories led to six warning topics: (1) risk of harm to mental health and psychological functioning; (2) risk of operating machinery while under the influence; (3) short-term physical side effects; (4) responsible use; (5) long-term negative physical effects; and (6) dependence, addiction, or abuse. The user-suggested warnings overlapped with six expert-recommended warnings identified in prior survey research and included two content areas that did not feature in expert-recommended warnings: short-term physical side effects and the importance of responsible use. Conclusions: The results are consistent with prior findings that some youths perceive cannabis use as potentially harmful. The current findings provide possible new content for warnings on cannabis packages. PMID:28861495

US Adult Illicit Cannabis Use, Cannabis Use Disorder, and Medical Marijuana Laws

PubMed Central

Sarvet, Aaron L.; Cerdá, Magdalena; Keyes, Katherine M.; Stohl, Malka; Galea, Sandro; Wall, Melanie M.

2017-01-01

Importance Over the last 25 years, illicit cannabis use and cannabis use disorders have increased among US adults, and 28 states have passed medical marijuana laws (MML). Little is known about MML and adult illicit cannabis use or cannabis use disorders considered over time. Objective To present national data on state MML and degree of change in the prevalence of cannabis use and disorders. Design, Participants, and Setting Differences in the degree of change between those living in MML states and other states were examined using 3 cross-sectional US adult surveys: the National Longitudinal Alcohol Epidemiologic Survey (NLAES; 1991-1992), the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; 2001-2002), and the National Epidemiologic Survey on Alcohol and Related Conditions–III (NESARC-III; 2012-2013). Early-MML states passed MML between NLAES and NESARC (“earlier period”). Late-MML states passed MML between NESARC and NESARC-III (“later period”). Main Outcomes and Measures Past-year illicit cannabis use and DSM-IV cannabis use disorder. Results Overall, from 1991-1992 to 2012-2013, illicit cannabis use increased significantly more in states that passed MML than in other states (1.4–percentage point more; SE, 0.5; P = .004), as did cannabis use disorders (0.7–percentage point more; SE, 0.3; P = .03). In the earlier period, illicit cannabis use and disorders decreased similarly in non-MML states and in California (where prevalence was much higher to start with). In contrast, in remaining early-MML states, the prevalence of use and disorders increased. Remaining early-MML and non-MML states differed significantly for use (by 2.5 percentage points; SE, 0.9; P = .004) and disorder (1.1 percentage points; SE, 0.5; P = .02). In the later period, illicit use increased by the following percentage points: never-MML states, 3.5 (SE, 0.5); California, 5.3 (SE, 1.0); Colorado, 7.0 (SE, 1.6); other early-MML states, 2.6 (SE

Factors determining yield and quality of illicit indoor cannabis (Cannabis spp.) production.

PubMed

Vanhove, Wouter; Van Damme, Patrick; Meert, Natalie

2011-10-10

Judiciary currently faces difficulties in adequately estimating the yield of illicit indoor cannabis plantations. The latter data is required in penalization which is based on the profits gained. A full factorial experiment in which two overhead light intensities, two plant densities and four varieties were combined in the indoor cultivation of cannabis (Cannabis spp.) was used to reveal cannabis drug yield and quality under each of the factor combinations. Highest yield was found for the Super Skunk and Big Bud varieties which also exhibited the highest concentrations of Δ(9)-tetrahydrocannabinol (THC). Results show that plant density and light intensity are additive factors whereas the variety factor significantly interacts with both plant density and light intensity factors. Adequate estimations of yield of illicit, indoor cannabis plantations can only be made if upon seizure all factors considered in this study are accounted for. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Terpene synthases from Cannabis sativa.

PubMed

Booth, Judith K; Page, Jonathan E; Bohlmann, Jörg

2017-01-01

Cannabis (Cannabis sativa) plants produce and accumulate a terpene-rich resin in glandular trichomes, which are abundant on the surface of the female inflorescence. Bouquets of different monoterpenes and sesquiterpenes are important components of cannabis resin as they define some of the unique organoleptic properties and may also influence medicinal qualities of different cannabis strains and varieties. Transcriptome analysis of trichomes of the cannabis hemp variety 'Finola' revealed sequences of all stages of terpene biosynthesis. Nine cannabis terpene synthases (CsTPS) were identified in subfamilies TPS-a and TPS-b. Functional characterization identified mono- and sesqui-TPS, whose products collectively comprise most of the terpenes of 'Finola' resin, including major compounds such as β-myrcene, (E)-β-ocimene, (-)-limonene, (+)-α-pinene, β-caryophyllene, and α-humulene. Transcripts associated with terpene biosynthesis are highly expressed in trichomes compared to non-resin producing tissues. Knowledge of the CsTPS gene family may offer opportunities for selection and improvement of terpene profiles of interest in different cannabis strains and varieties.

Rapid isolation procedure for Δ9-tetrahydrocannabinolic acid A (THCA) from Cannabis sativa using two flash chromatography systems.

PubMed

Wohlfarth, Ariane; Mahler, Hellmut; Auwärter, Volker

2011-10-15

Two isolation procedures for Δ9-tetrahydrocannabinolic acid A (THCA), the biogenetic precursor in the biosynthesis of the psychoactive Δ9-tetrahydrocannabinol (THC) in the cannabis plant, are presented. Two flash chromatography systems that can be used independently from each other were developed to separate THCA from other compounds of a crude cannabis extract. In both systems UV absorption at 209 and 270 nm was monitored. Purity was finally determined by HPLC-DAD, NMR and GC-MS analysis with a focus on the impurity THC. System 1 consisted of a normal phase silica column (120 g) as well as cyclohexane and acetone--both spiked with the modifier pyridine--as mobile phases. Gradient elution was performed over 15 min. After the chromatographic run the fractions containing THCA fractions were pooled, extracted with hydrochloric acid to eliminate pyridine and evaporated to dryness. Loading 1800 mg cannabis extract yielded 623 mg THCA with a purity of 99.8% and a THC concentration of 0.09%. System 2 was based on a reversed-phase C18 column (150 g) combined with 0.55% formic acid and methanol as mobile phases. A very flat gradient was set over 20 minutes. After pooling the THCA-containing fractions methanol was removed in a rotary evaporator. THCA was re-extracted from the remaining aqueous phase with methyl tert-butyl ether. The organic phase was finally evaporated under high vacuum conditions. Loading 300 mg cannabis extract yielded 51 mg THCA with a purity of 98.8% and a THC concentration of 0.67%. Copyright © 2011 Elsevier B.V. All rights reserved.

Approach-bias predicts development of cannabis problem severity in heavy cannabis users: results from a prospective FMRI study.

PubMed

Cousijn, Janna; Goudriaan, Anna E; Ridderinkhof, K Richard; van den Brink, Wim; Veltman, Dick J; Wiers, Reinout W

2012-01-01

A potentially powerful predictor for the course of drug (ab)use is the approach-bias, that is, the pre-reflective tendency to approach rather than avoid drug-related stimuli. Here we investigated the neural underpinnings of cannabis approach and avoidance tendencies. By elucidating the predictive power of neural approach-bias activations for future cannabis use and problem severity, we aimed at identifying new intervention targets. Using functional Magnetic Resonance Imaging (fMRI), neural approach-bias activations were measured with a Stimulus Response Compatibility task (SRC) and compared between 33 heavy cannabis users and 36 matched controls. In addition, associations were examined between approach-bias activations and cannabis use and problem severity at baseline and at six-month follow-up. Approach-bias activations did not differ between heavy cannabis users and controls. However, within the group of heavy cannabis users, a positive relation was observed between total lifetime cannabis use and approach-bias activations in various fronto-limbic areas. Moreover, approach-bias activations in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) independently predicted cannabis problem severity after six months over and beyond session-induced subjective measures of craving. Higher DLPFC/ACC activity during cannabis approach trials, but lower activity during cannabis avoidance trials were associated with decreases in cannabis problem severity. These findings suggest that cannabis users with deficient control over cannabis action tendencies are more likely to develop cannabis related problems. Moreover, the balance between cannabis approach and avoidance responses in the DLPFC and ACC may help identify individuals at-risk for cannabis use disorders and may be new targets for prevention and treatment.

Approach-Bias Predicts Development of Cannabis Problem Severity in Heavy Cannabis Users: Results from a Prospective FMRI Study

PubMed Central

Cousijn, Janna; Goudriaan, Anna E.; Ridderinkhof, K. Richard; van den Brink, Wim; Veltman, Dick J.; Wiers, Reinout W.

2012-01-01

A potentially powerful predictor for the course of drug (ab)use is the approach-bias, that is, the pre-reflective tendency to approach rather than avoid drug-related stimuli. Here we investigated the neural underpinnings of cannabis approach and avoidance tendencies. By elucidating the predictive power of neural approach-bias activations for future cannabis use and problem severity, we aimed at identifying new intervention targets. Using functional Magnetic Resonance Imaging (fMRI), neural approach-bias activations were measured with a Stimulus Response Compatibility task (SRC) and compared between 33 heavy cannabis users and 36 matched controls. In addition, associations were examined between approach-bias activations and cannabis use and problem severity at baseline and at six-month follow-up. Approach-bias activations did not differ between heavy cannabis users and controls. However, within the group of heavy cannabis users, a positive relation was observed between total lifetime cannabis use and approach-bias activations in various fronto-limbic areas. Moreover, approach-bias activations in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) independently predicted cannabis problem severity after six months over and beyond session-induced subjective measures of craving. Higher DLPFC/ACC activity during cannabis approach trials, but lower activity during cannabis avoidance trials were associated with decreases in cannabis problem severity. These findings suggest that cannabis users with deficient control over cannabis action tendencies are more likely to develop cannabis related problems. Moreover, the balance between cannabis approach and avoidance responses in the DLPFC and ACC may help identify individuals at-risk for cannabis use disorders and may be new targets for prevention and treatment. PMID:22957019

Cannabis smoke condensate III: the cannabinoid content of vaporised Cannabis sativa.

PubMed

Pomahacova, B; Van der Kooy, F; Verpoorte, R

2009-11-01

Cannabis sativa is a well-known recreational drug and, as such, a controlled substance of which possession and use are illegal in most countries of the world. Due to the legal constraints on the possession and use of C. sativa, relatively little research on the medicinal qualities of this plant has been conducted. Interest in the medicinal uses of this plant has, however, increased in the last decades. The methods of administration for medicinal purposes are mainly through oral ingestion, smoking, and nowadays also inhalation through vaporization. During this study the commercially available Volcano vaporizing device was compared with cannabis cigarette smoke. The cannabis smoke and vapor (obtained at different temperatures) were quantitatively analyzed by high-performance liquid chromatography (HPLC). In addition, different quantities of cannabis material were also tested with the vaporizer. The cannabinoids:by-products ratio in the vapor obtained at 200 degrees C and 230 degrees C was significantly higher than in the cigarette smoke. The worst ratio of cannabinoids:by-products was obtained from the vaporized cannabis sample at 170 degrees C.

Therapeutic Use of Δ9-THC and Cannabidiol: Evaluation of a New Extraction Procedure for the Preparation of Cannabis-based Olive Oil.

PubMed

Morini, Luca; Porro, Giorgio; Liso, Maurizio; Groppi, Angelo

2017-01-01

Since 2013 Cannabis-based preparations, containing the two main cannabinoids of interest, Δ9-tetrahydrocannabinol (THC), and cannabidiol (CBD), can be used for therapeutic purposes, such as palliative care, neurodegenerative disorder treatment and other therapies. The preparations may consist of a drug partition in sachets, capsules or through the extraction in certified olive oil. The aims of the study were: a) to develop and validate a new liquid chromatographictandem mass spectrometric (LC-MS/MS) method for the identification and quantification of THC and CBD in olive oil; b) to evaluate the extraction efficiency and reproducibility of a new commercial extractor on the market. The olive oil was simply diluted three consecutive times, using organic solvents with increasing polarity index (n-hexane → isopropanol → methanol). The sample was then directly injected into LC-MS/MS system, operating in Multiple Reaction Monitoring Mode, in positive polarization. The method was then fully validated. The method assessed to be linear over the range 0.1-10 ng/µL for both THC and CBD. Imprecision and accuracy were within 12.2% and 16.9% respectively; matrix effects proved to be negligible; THC concentration in oil is stable up to two months at room temperature, whenever kept in the dark. CBD provided a degradation of 30% within ten weeks. The method was then applied to olive oil after sample preparation, in order to evaluate the efficiency of extraction of a new generation instrument. Temperature of extraction is the most relevant factor to be optimized. Indeed, a difference of 2°C (from 94.5°C to 96.5°C, the highest temperature reached in the experiments) of the heating phase, increases the percentage of extraction from 54.2% to 64.0% for THC and from 58.2% to 67.0% for CBD. The amount of THC acid and CBD acid that are decarboxylated during the procedure must be check out in the future. The developed method was simple and fast. The extraction procedure proved to be

Sex differences in cannabis withdrawal symptoms among treatment-seeking cannabis users

PubMed Central

Herrmann, Evan S.; Weerts, Elise M.; Vandrey, Ryan

2015-01-01

Over 300,000 individuals enter treatment for cannabis use disorders (CUDs) in the U.S. annually. Cannabis withdrawal is associated with poor CUD treatment outcomes, but no prior studies have examined sex differences in withdrawal among treatment-seeking cannabis users. Treatment-seeking cannabis users (45 women and 91 men) completed a Marijuana Withdrawal Checklist (MWC) at treatment intake to retrospectively characterize withdrawal symptoms experienced during their most recent quit attempt. Composite Withdrawal Discomfort Scale (WDS) scores were calculated using the 14 items on the MWC that correspond to valid cannabis withdrawal symptoms described in DSM-5. Demographic and substance use characteristics, overall WDS scores, and scores on individual WDS symptoms were compared between women and men. Women had higher overall WDS scores than men, and women had higher scores than men on six individual symptoms in two domains, mood symptoms (irritability, restlessness, increased anger, violent outbursts) and gastrointestinal symptoms (nausea, stomach pain). Follow-up analyses isolating the incidence and severity of WDS symptoms demonstrated that women generally reported a higher number of individual withdrawal symptoms than men, and that they reported experiencing some symptoms as more severe. This is the first report to demonstrate that women seeking treatment for CUDs may experience more withdrawal then men during quit attempts. Prospective studies of sex differences in cannabis withdrawal are warranted. PMID:26461168

Cannabis Use Frequency and Use-Related Impairment among African American and White Users: The Impact of Cannabis Use Motives

PubMed Central

Shah, Sonia M.; Dean, Kimberlye E.; Zvolensky, Michael J.

2015-01-01

Objectives Cannabis use motives are differentially related to cannabis-related impairment and coping motives appear to have the strongest relation to use-related impairment. However, it is currently unknown whether African American individuals differ from White persons in reasons for using cannabis. It is also unknown whether motives’ relations to cannabis use and related impairment vary as a function of race. The present study examined the role of race on cannabis use motives and tested whether motives’ relations with cannabis use and related impairment differed by race. Design The sample consisted of 111 (67.6% non-Hispanic White, 32.4% African American) current cannabis-using adults. Results African American participants did not significantly differ from White participants on cannabis use frequency or use-related impairment. African American participants endorsed more social motives than White participants. Race interacted with social, coping, and conformity motives to predict cannabis-related impairment such that these motives were positively related to cannabis impairment among African American, but not White, participants. Conclusion Although African American and White participants do not differ in their cannabis use frequency or cannabis-related impairment, they appear to use cannabis for different reasons. Further, conformity, coping, and social motives were differentially associated with cannabis-related impairment as a function of race. Findings suggest motives for cannabis use should be contexualized in the context of race. PMID:26264291

Cannabis use frequency and use-related impairment among African-American and White users: the impact of cannabis use motives.

PubMed

Buckner, Julia D; Shah, Sonia M; Dean, Kimberlye E; Zvolensky, Michael J

2016-01-01

Cannabis use motives are differentially related to cannabis-related impairment and coping motives appear to have the strongest relation to use-related impairment. However, it is currently unknown whether African-American individuals differ from White persons in reasons for using cannabis. It is also unknown whether motives' relations to cannabis use and related impairment vary as a function of race. The present study examined the role of race on cannabis use motives and tested whether motives' relations with cannabis use and related impairment differed by race. The sample consisted of 111 (67.6% non-Hispanic White, 32.4% African-American) current cannabis-using adults. African-American participants did not significantly differ from White participants on cannabis use frequency or use-related impairment. African-American participants endorsed more social motives than White participants. Race interacted with social, coping, and conformity motives to predict cannabis-related impairment such that these motives were positively related to cannabis impairment among African-American, but not White, participants. Although African-American and White participants do not differ in their cannabis use frequency or cannabis-related impairment, they appear to use cannabis for different reasons. Further, conformity, coping, and social motives were differentially associated with cannabis-related impairment as a function of race. Findings suggest motives for cannabis use should be contexualised in the context of race.

Substituting cannabis for prescription drugs, alcohol and other substances among medical cannabis patients: The impact of contextual factors.

PubMed

Lucas, Philippe; Walsh, Zach; Crosby, Kim; Callaway, Robert; Belle-Isle, Lynne; Kay, Robert; Capler, Rielle; Holtzman, Susan

2016-05-01

Recent years have witnessed increased attention to how cannabis use impacts the use of other psychoactive substances. The present study examines the use of cannabis as a substitute for alcohol, illicit substances and prescription drugs among 473 adults who use cannabis for therapeutic purposes. The Cannabis Access for Medical Purposes Survey is a 414-question cross-sectional survey that was available to Canadian medical cannabis patients online and by hard copy in 2011 and 2012 to gather information on patient demographics, medical conditions and symptoms, patterns of medical cannabis use, cannabis substitution and barriers to access to medical cannabis. Substituting cannabis for one or more of alcohol, illicit drugs or prescription drugs was reported by 87% (n = 410) of respondents, with 80.3% reporting substitution for prescription drugs, 51.7% for alcohol, and 32.6% for illicit substances. Respondents who reported substituting cannabis for prescription drugs were more likely to report difficulty affording sufficient quantities of cannabis, and patients under 40 years of age were more likely to substitute cannabis for all three classes of substance than older patients. The finding that cannabis was substituted for all three classes of substances suggests that the medical use of cannabis may play a harm reduction role in the context of use of these substances, and may have implications for abstinence-based substance use treatment approaches. Further research should seek to differentiate between biomedical substitution for prescription pharmaceuticals and psychoactive drug substitution, and to elucidate the mechanisms behind both. [Lucas P, Walsh Z, Crosby K, Callaway R, Belle-Isle L, Kay B, Capler R, Holtzman S. Substituting cannabis for prescription drugs, alcohol, and other substances among medical cannabis patients: The impact of contextual factors. Drug Alcohol Rev 2016;35:326-333]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

The association between perceived distress tolerance and cannabis use problems, cannabis withdrawal symptoms, and self-efficacy for quitting cannabis: The explanatory role of pain-related affective distress.

PubMed

Manning, Kara; Rogers, Andrew H; Bakhshaie, Jafar; Hogan, Julianna B D; Buckner, Julia D; Ditre, Joseph W; Zvolensky, Michael J

2018-10-01

Rates of cannabis use and related problems continue to rise, ranking as the third most common substance use disorder in the United States, behind tobacco and alcohol use. Past work suggests that perceived distress tolerance is related to several clinically significant features of cannabis use (e.g., coping-oriented use). However, there has been little exploration of the mechanisms that may underlie relations between perceived distress tolerance and cannabis use problems, withdrawal severity, and self-efficacy for quitting. The current study sought to examine the experience of pain, which frequently co-occurs with cannabis use (Ashrafioun, Bohnert, Jannausch, & Ilgen, 2015), as an underlying factor in the relation between perceived distress tolerance and cannabis related problems among 203 current cannabis-using adults (29.2% female, M = 37.7 years, SD = 10.2, 63% African American). Results indicated that perceived distress tolerance via pain related affective distress significantly predicted the severity of cannabis use problems (Pm = 0.60), degree of cannabis withdrawal (Pm = 0.39), and lower self-efficacy for quitting cannabis (Pm = 0.36). Future work may usefully explore the role of pain-related affective distress as a mechanistic factor in the context of perceived distress tolerance-cannabis relations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of reclassification of cannabis on hospital admissions for cannabis psychosis: a time series analysis.

PubMed

Hamilton, Ian; Lloyd, Charlie; Hewitt, Catherine; Godfrey, Christine

2014-01-01

The UK Misuse of Drugs Act (1971) divided controlled drugs into three groups A, B and C, with descending criminal sanctions attached to each class. Cannabis was originally assigned by the Act to Group B but in 2004, it was transferred to the lowest risk group, Group C. Then in 2009, on the basis of increasing concerns about a link between high strength cannabis and schizophrenia, it was moved back to Group B. The aim of this study is to test the assumption that changes in classification lead to changes in levels of psychosis. In particular, it explores whether the two changes in 2004 and 2009 were associated with changes in the numbers of people admitted for cannabis psychosis. An interrupted time series was used to investigate the relationship between the two changes in cannabis classification and their impact on hospital admissions for cannabis psychosis. Reflecting the two policy changes, two interruptions to the time series were made. Hospital Episode Statistics admissions data was analysed covering the period 1999 through to 2010. There was a significantly increasing trend in cannabis psychosis admissions from 1999 to 2004. However, following the reclassification of cannabis from B to C in 2004, there was a significant change in the trend such that cannabis psychosis admissions declined to 2009. Following the second reclassification of cannabis back to class B in 2009, there was a significant change to increasing admissions. This study shows a statistical association between the reclassification of cannabis and hospital admissions for cannabis psychosis in the opposite direction to that predicted by the presumed relationship between the two. However, the reasons for this statistical association are unclear. It is unlikely to be due to changes in cannabis use over this period. Other possible explanations include changes in policing and systemic changes in mental health services unrelated to classification decisions. Copyright © 2013 Elsevier B.V. All rights

Cannabis use and first manic episode.

PubMed

Bally, Nathalie; Zullino, Daniele; Aubry, Jean-Michel

2014-08-01

Cannabis is the most commonly abused drug among patients with bipolar disorder. Available data has shown that the risk of psychotic disorders increases with the frequency and intensity of cannabis abuse. The present purpose was to review relevant studies to investigate whether cannabis use can be linked to the onset of mania in bipolar disorder. Articles published between 1972 and December 2013 were searched on Medline and PsychInfo using the following keywords: first manic episode, or onset mania, or bipolar disorder and cannabis. Relevant papers cited in the references of selected articles were further considered for inclusion into the review. Lifetime use of cannabis among bipolar patients appears to be around 70% and approximately 30% of patients with a bipolar disorder present a comorbidity of cannabis abuse or dependence. Cannabis use is associated with younger age at onset of first mania and with more frequent depressive or manic episodes, although the evidence is somewhat inconsistent. Likewise cannabis consumption is related to poorer outcome and an increased risk of rapid cycling or mixed episodes. In contrast, neuro-cognitive functioning seems to be positively affected in patients with psychiatric comorbidity. While cannabis use often precedes first manic episodes, the causal direction remains to be determined. Variations in definition of cannabis use/dependence. Lack of controlled studies limiting definite conclusions about a putative causal relationship between cannabis and onset of mania. Further investigations are needed to clarify the relationships between cannabis use and first manic episode. Copyright © 2014 Elsevier B.V. All rights reserved.

Cannabis Mobile Apps: A Content Analysis

PubMed Central

Popova, Lucy; Grana, Rachel; Zhao, Shirley; Chavez, Kathryn

2015-01-01

Background Mobile technology is pervasive and widely used to obtain information about drugs such as cannabis, especially in a climate of rapidly changing cannabis policy; yet the content of available cannabis apps is largely unknown. Understanding the resources available to those searching for cannabis apps will clarify how this technology is being used to reflect and influence cannabis use behavior. Objective We investigated the content of 59 cannabis-related mobile apps for Apple and Android devices as of November 26, 2014. Methods The Apple and Google Play app stores were searched using the terms “cannabis” and “marijuana.” Three trained coders classified the top 20 apps for each term and each store, using a coding guide. Apps were examined for the presence of 20 content codes derived by the researchers. Results Total apps available for each search term were 124 for cannabis and 218 for marijuana in the Apple App Store, and 250 each for cannabis and marijuana on Google Play. The top 20 apps in each category in each store were coded for 59 independent apps (30 Apple, 29 Google Play). The three most common content areas were cannabis strain classification (33.9%), facts about cannabis (20.3%), and games (20.3%). In the Apple App Store, most apps were free (77%), all were rated “17+” years, and the average user rating was 3.9/5 stars. The most popular apps provided cannabis strain classifications (50%), dispensary information (27%), or general facts about cannabis (27%). Only one app (3%) provided information or resources related to cannabis abuse, addiction, or treatment. On Google Play, most apps were free (93%), rated “high maturity” (79%), and the average user rating was 4.1/5. The most popular app types offered games (28%), phone utilities (eg, wallpaper, clock; 21%) and cannabis food recipes (21%); no apps addressed abuse, addiction, or treatment. Conclusions Cannabis apps are generally free and highly rated. Apps were most often informational

Abnormal medial prefrontal cortex activity in heavy cannabis users during conscious emotional evaluation.

PubMed

Wesley, Michael J; Lile, Joshua A; Hanlon, Colleen A; Porrino, Linda J

2016-03-01

Long-term heavy cannabis users (cannabis users) who are not acutely intoxicated have diminished subconscious neural responsiveness to affective stimuli. This study sought to determine if abnormal processing extends to the conscious evaluation of emotional stimuli. Functional magnetic resonance imaging (fMRI) was used to examine brain activity as cannabis users (N = 16) and non-cannabis-using controls (N = 17) evaluated and categorized standardized International Affective Picture System (IAPS) stimuli. Individual judgments were used to isolate activity during the evaluation of emotional (i.e., emotional evaluation) or neutral (i.e., neutral evaluation) stimuli. Within- and between-group analyses were performed. Both groups judged the same stimuli as emotional and had activations in visual, midbrain, and middle cingulate cortices during emotional evaluation, relative to neutral. Within-group analyses also revealed amygdalar and inferior frontal gyrus activations in controls, but not cannabis users, and medial prefrontal cortex (mPFC) deactivations in cannabis users, but not controls, during emotional evaluation, relative to neutral. Between-group comparisons found that mPFC activity during positive and negative evaluation was significantly hypoactive in cannabis users, relative to controls. Abnormal neural processing of affective content extends to the level of consciousness in cannabis users. The hypoactive mPFC responses observed resembles the attenuated mPFC responses found during increased non-affective cognitive load in prior research. These findings suggest that abnormal mPFC singling in cannabis users during emotional evaluation might be associated with increased non-affective cognitive load.

[Related, induced and associated psychiatric disorders to cannabis].

PubMed

Laqueille, Xavier

2005-01-15

Cannabis disorders, according to the DSM-IV and the ICD-10 criteria, include cannabis intoxication, cannabis abuse, cannabis dependence, and cannabis-related disorders (anxiety disorders, psychotic disorders, cannabis intoxication delirium). Although cannabis withdrawal syndrome has clinical importance, it is not included in these classifications. The amotivational syndrome remains controversial. The psychiatric disorders related to cannabis use are anxiety disorders, depressive disorders and psychotic disorders. Cannabis use could be closely linked with the neurobiology of schizophrenia. As the other psychoactive substances, cannabis use worsens the psychiatric outcomes and is associated with poorer treatment compliance.

[Consumption of cannabis in adolescents].

PubMed

Phan, O; Obradovic, I; Har, A

2017-01-01

Over the past 10 years, the consumption of cannabis among adolescents has dramatically increased. Today, adolescent cannabis use is a major public health problem. Two forms of cannabis are commonly smoked: herb (marijuana) and resin. These forms have a high concentration of tetrahydrocannabinol, the active molecule of cannabis. Recent research has helped understand how the cannabinoid system works. This system combines specific receptors and specific molecules: the endocannabinoids. The effects of cannabis use are now well documented. Some adolescents report subjective positive effects. They use it not only on a recreational basis, but also to deal with their emotions. Over the long term, cannabis increases the risk of depression and schizophrenia for those adolescents who are at risk. Use, misuse, and dependence are frequently associated with heavy psychopathologic problems such as vulnerability and depression. Many cannabis dependence psychotherapies have shown their efficacy and efficiency. Motivational interviews, cognitive behavioral therapy, multidimensional family therapy (MDFT), and residential treatment have proved highly effective. MDFT seems very effective, especially in cases of heavy use. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Terpene synthases from Cannabis sativa

PubMed Central

Booth, Judith K.; Page, Jonathan E.

2017-01-01

Cannabis (Cannabis sativa) plants produce and accumulate a terpene-rich resin in glandular trichomes, which are abundant on the surface of the female inflorescence. Bouquets of different monoterpenes and sesquiterpenes are important components of cannabis resin as they define some of the unique organoleptic properties and may also influence medicinal qualities of different cannabis strains and varieties. Transcriptome analysis of trichomes of the cannabis hemp variety ‘Finola’ revealed sequences of all stages of terpene biosynthesis. Nine cannabis terpene synthases (CsTPS) were identified in subfamilies TPS-a and TPS-b. Functional characterization identified mono- and sesqui-TPS, whose products collectively comprise most of the terpenes of ‘Finola’ resin, including major compounds such as β-myrcene, (E)-β-ocimene, (-)-limonene, (+)-α-pinene, β-caryophyllene, and α-humulene. Transcripts associated with terpene biosynthesis are highly expressed in trichomes compared to non-resin producing tissues. Knowledge of the CsTPS gene family may offer opportunities for selection and improvement of terpene profiles of interest in different cannabis strains and varieties. PMID:28355238

Cannabis induced asystole.

PubMed

Brancheau, Daniel; Blanco, Jessica; Gholkar, Gunjan; Patel, Brijesh; Machado, Christian

2016-01-01

Cannabis or marijuana is the most used recreational, and until recently illegal, drug in the United States. Although cannabis has medicinal use, its consumption has been linked to motor vehicle accidents in dose dependent fashion. Marijuana and other cannabinoids produce a multitude of effects on the human body that may result in these motor vehicle accidents. Some of the effects that marijuana has been known to cause include altered sensorium, diminished reflexes, and increased vagal tone. We present a case of cannabis induced asystole from hypervagotonia. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of age at onset of cannabis use on cannabis dependence and driving under the influence in the United States.

PubMed

Le Strat, Yann; Dubertret, Caroline; Le Foll, Bernard

2015-03-01

There is growing evidence that driving under the influence of cannabis is associated with a higher risk of motor vehicle crash. Cannabis dependence has been reported to be associated with a three-fold increased risk of motor vehicle crash. The impact of the age at onset of cannabis use on the risk of both cannabis dependence and driving under the influence of cannabis has not been evaluated so far. Data were drawn from the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a survey of 43,093 adults aged 18 years and older. We limited our analyses to the sample of participants who reported having ever used cannabis (n=8172), of whom 8068 had a known age at onset of cannabis use. Of the 8068 participants included, 5.15% reported having driven under the influence of cannabis. Among those, only a minority (14.46%) were diagnosed with cannabis dependence. Compared to those who start using cannabis at age 21 years or after, participants who used cannabis before the age of 14 years were 4 times more likely to have a history of cannabis dependence and 3 times more likely to reported having driven under the influence of cannabis. An inverse relationship between the age at onset of cannabis use and driving under the influence and risk of cannabis dependence was found. Starting to smoke cannabis younger than 21 years is associated with both cannabis dependence and driving under the influence of cannabis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cannabis Use in Palliative Oncology: A Review of the Evidence for Popular Indications.

PubMed

Turgeman, Ilit; Bar-Sela, Gil

2017-02-01

A flowering plant of variegated ingredients and psychoactive qualities, cannabis has long been used for medicinal and recreational purposes. Currently, cannabis is approved in several countries for indications of symptomatic alleviation. However, limited knowledge on the benefits and risks precludes inclusion of cannabis in standard treatment guidelines. This review provides a summary of the available literature on the use of cannabis and cannabinoid-based medicines in palliative oncology. Favorable outcomes are demonstrated for chemotherapy-induced nausea and vomiting and cancer-related pain, with evidence of advantageous neurological interactions. Benefit in the treatment of anorexia, insomnia and anxiety is also suggested. Short- and long-term side effects appear to be manageable and to subside after discontinuation of the drug. Finally, cannabinoids have shown anti-neoplastic effects in preclinical studies in a wide range of cancer cells and some animal models. Further research is needed before cannabis can become a part of evidence-based oncology practice.

Sociodemographic Characteristics of Cannabis Smokers and the Experience of Cannabis Withdrawal

PubMed Central

Copersino, Marc L.; Boyd, Susan J.; Tashkin, Donald P.; Huestis, Marilyn A.; Heishman, Stephen J.; Dermand, John C.; Simmons, Michael S.; Gorelick, David A.

2011-01-01

Background Cannabis withdrawal can be a negative reinforcer for relapse, but little is known about its association with demographic characteristics. Objectives Evaluate the association of demographic characteristics with the experience of cannabis withdrawal. Methods Retrospective self-report of a “serious” cannabis quit attempt without formal treatment in a convenience sample of 104 non-treatment-seeking, adult cannabis smokers (mean age 35 years, 52% white, 78% male) with no other current substance use disorder (except tobacco) or chronic health problems. Reasons for quitting, coping strategies to help quit, and 18 specific withdrawal symptoms were assessed by questionaire. Results Among withdrawal symptoms, only anxiety, increased sex drive, and craving showed significant associations with age, race, or sex. Women were more likely than men to report a physical withdrawal symptom (OR = 3.2, 95% CI = .99–10.4, p = .05), especially upset stomach. There were few significant demographic associations with coping strategies or reasons for quitting. Conclusions and Scientific Significance This small study suggests that there are few robust associations between demographic characteristics and cannabis withdrawal. Future studies with larger samples are needed. Attention to physical withdrawal symptoms in women may help promote abstinence. PMID:20678028

The effect of hydroalcoholic extract of Cannabis Sativa on appetite hormone in rat.

PubMed

Mazidi, Mohsen; Baghban Taraghdari, Sara; Rezaee, Peyman; Kamgar, Maryam; Jomezadeh, Mohammad Reza; Akbarieh Hasani, Omid; Soukhtanloo, Mohammad; Hosseini, Mahmoud; Gholamnezhad, Zahra; Rakhshandeh, Hassan; Norouzy, Abdolreza; Esmaily, Habibollah; Patterson, Michael; Nematy, Mohsen

2014-12-01

Ghrelin is an orexigenic peptide which is secreted from stomach. Cannabis sativa is known as an orexigenic herb in Iranian traditional medicine. Little evidence is published about its effect on energy intake and its mechanism. In the current study, the possible effect of hydroalcoholic extract of C. sativa on appetite and ghrelin is evaluated. Thirty male Wistar rats were randomly divided into five groups. Two control groups were selected, the first group received 0.5 mL water per day (vehicle group) and another group did not receive anything (control group). The other three groups were treated daily with 50, 100 or 150 mg/kg of C. sativa for 7 days, respectively. Daily energy intake of the rats was calculated for 10 days prior to the> intervention and for the 7 day intervention. To investigate changes in plasma ghrelin as a potential mechanism, an orexigenic dose (150 mg/kg) of C. sativa or distilled water (vehicle) was fed to two separate groups of six rats by gavage. Total ghrelin levels in plasma were measured for 3 h post-gavage. There was no significant difference in energy intake between control and vehicle groups. Treatment with 100 and 150 mg/kg of the extract significantly increased energy intake vs the other groups (p<0.05). Total ghrelin levels were significantly elevated in the C. sativa group vs vehicle 30 and 60 min post-gavage. This study showed that C. sativa had both positive and dose-related effects on appetite of rats. Future studies are warranted to evaluate the orexigenic effect of this plant in human.

Perceived support for medical cannabis use among approved medical cannabis users in Canada.

PubMed

Leos-Toro, Cesar; Shiplo, Samantha; Hammond, David

2018-06-05

Very little is known about the social experience of medical cannabis use, including the experience of stigma among approved users. The current study examined perceptions of support from physicians, family and friends as well as the prevalence of 'hiding' medicinal cannabis use. An online cross-sectional survey (N = 276) was conducted from 29 April to 8 June 2015. No public sampling frame was available from which to sample approved medical cannabis users (MCU). Eligible respondents were approved MCUs, aged 18 years or older, and reported cannabis use in the past 30 days for health reasons. Logistic regression analyses were used to assess aspects of stigma, including perceived support from their immediate social environment as well as behaviours reflecting a perceived social disapproval. Approximately one-third of respondents (32.6%) reported that their physician had refused to provide a medical document, and the vast majority of respondents (79.3%) reported hiding their medical cannabis use, most commonly to avoid judgement. Fewer than half of approved users perceived that their doctor was 'supportive' (38%), whereas two-thirds perceived support from family (66.3%) and friends (66.3%). Perceptions of support were similar across most socio-demographic sub-groups. Substantial proportions of approved MCUs in Canada report a lack of support and most have made some effort to conceal their medical cannabis use. Overall, the findings suggest that social norms around medical cannabis use remain unfavourable for many users, despite that fact that medical cannabis has been legal in Canada for more than a decade. © 2018 Australasian Professional Society on Alcohol and other Drugs.

Cannabis microbiome sequencing reveals several mycotoxic fungi native to dispensary grade Cannabis flowers

PubMed Central

McKernan, Kevin; Spangler, Jessica; Zhang, Lei; Tadigotla, Vasisht; Helbert, Yvonne; Foss, Theodore; Smith, Douglas

2016-01-01

The Center for Disease Control estimates 128,000 people in the U.S. are hospitalized annually due to food borne illnesses. This has created a demand for food safety testing targeting the detection of pathogenic mold and bacteria on agricultural products. This risk extends to medical Cannabis and is of particular concern with inhaled, vaporized and even concentrated Cannabis products . As a result, third party microbial testing has become a regulatory requirement in the medical and recreational Cannabis markets, yet knowledge of the Cannabis microbiome is limited. Here we describe the first next generation sequencing survey of the fungal communities found in dispensary based Cannabis flowers by ITS2 sequencing, and demonstrate the sensitive detection of several toxigenic Penicillium and Aspergillus species, including P. citrinum and P. paxilli, that were not detected by one or more culture-based methods currently in use for safety testing. PMID:27303623

Dutch coffee shops and trends in cannabis use.

PubMed

Korf, Dirk J

2002-01-01

Conflicting predictions have been made to the influence of decriminalization on cannabis use. Prohibitionists forecast that decriminalization will lead to an increase in consumption of cannabis, while their opponents hypothesise that cannabis use will decline after decriminalization. Most probably cannabis use in the Netherlands so far evolved in two waves, with a first peak around 1970, a low during the late 1970s and early 1980s, and a second peak in the mid-1990s. It is striking that this trend in cannabis use among youth in the Netherlands rather parallels four identified stages in the availability of cannabis. The number of cannabis users peaked when the cannabis was distributed through an underground market (late 1960s and early 1970s). Then the number decreased as house dealers were superseeding the underground market (1970s), and went up again after coffee shops took over the sale of cannabis (1980s), and stabilised or slightly decreased by the end of the 1990s when the number of coffee shops was reduced. Although changes in cannabis policy went along with changes in availability of cannabis and prevalence of cannabis use, it is questionable whether changes in cannabis policy were causally related to trends in cannabis use. Cannabis use also developed in waves in other European countries that did not decriminalize cannabis, as well as in the US. Consequently, trends in cannabis use seem to develop rather independently of cannabis policy.

Cannabis - from cultivar to chemovar.

PubMed

Hazekamp, A; Fischedick, J T

2012-01-01

The medicinal use of Cannabis is increasing as countries worldwide are setting up official programs to provide patients with access to safe sources of medicinal-grade Cannabis. An important question that remains to be answered is which of the many varieties of Cannabis should be made available for medicinal use. Drug varieties of Cannabis are commonly distinguished through the use of popular names, with a major distinction being made between Indica and Sativa types. Although more than 700 different cultivars have already been described, it is unclear whether such classification reflects any relevant differences in chemical composition. Some attempts have been made to classify Cannabis varieties based on chemical composition, but they have mainly been useful for forensic applications, distinguishing drug varieties, with high THC content, from the non-drug hemp varieties. The biologically active terpenoids have not been included in these approaches. For a clearer understanding of the medicinal properties of the Cannabis plant, a better classification system, based on a range of potentially active constituents, is needed. The cannabinoids and terpenoids, present in high concentrations in Cannabis flowers, are the main candidates. In this study, we compared cultivars obtained from multiple sources. Based on the analysis of 28 major compounds present in these samples, followed by principal component analysis (PCA) of the quantitative data, we were able to identify the Cannabis constituents that defined the samples into distinct chemovar groups. The study indicates the usefulness of a PCA approach for chemotaxonomic classification of Cannabis varieties. Copyright © 2012 John Wiley & Sons, Ltd.

Yield and turnover of illicit indoor cannabis (Cannabis spp.) plantations in Belgium.

PubMed

Vanhove, Wouter; Surmont, Tim; Van Damme, Patrick; De Ruyver, Brice

2012-07-10

In prosecution, Belgian judiciary currently uses outdated yield figures (28.1g per plant, sold at € 3/g at grower level) for fining illicit indoor cannabis plantations. Using state-of-the-art cultivation techniques, our growth experiments showed that yield is better expressed in g/m(2) cultivated surface area rather than in g per plant, and that yield varies significantly between different cannabis strains. It was found that the lower-bound of the one-sided 95% confidence interval of the yield of an indoor cannabis plantation can be set at 575 g/m(2). Prices and pricing mechanisms were investigated using interviews with respondents selected through snowball sampling. Results reveal that (i) the Belgian cannabis market chain is highly complex; (ii) unit prices are predominantly determined by transaction sizes; but also (iii) a set of product- and socially-related price-fixing mechanisms have an equally important role. At grower level, respondents reported prices for 1 g of dry cannabis buds to range € 3.00-4.25. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Cannabis can augment thrombolytic properties of rtPA: Intracranial hemorrhage in a heavy cannabis user.

PubMed

Shere, Amar; Goyal, Hemant

2017-12-01

Cannabis is one of the most commonly used illicit drugs in the United States and is considered to have several adverse health effects. There is evidence suggesting that its recreational use is associated with both increased cardio- and cerebrovascular events. Recently, multiple cases of ischemic and hemorrhagic strokes associated with cannabis use were reported in the literature (Goyal et al., 2017). It has been suggested that cannabis can affect cerebral auto-regulation and vascular tone leading to vasoconstriction and acute ischemic stroke. However, hemorrhagic strokes, which are often seen with sympathomimetic illicit drugs (e.g. cocaine and amphetamines), have rarely been reported due to cannabis. Many cellular mechanisms within non-ischemic tissue post stroke may be augmented by heavy cannabis use. Here, we describe a rapid development of hemorrhage following thrombolytic therapy in a patient with heavy cannabis use with an ischemic stroke. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of extended cannabis abstinence on clinical symptoms in cannabis dependent schizophrenia patients versus non-psychiatric controls.

PubMed

Rabin, Rachel A; Kozak, Karolina; Zakzanis, Konstantine K; Remington, Gary; George, Tony P

2018-04-01

Rates of cannabis use among patients with schizophrenia are high, however little is understood about clinical effects of continued cannabis use and cessation after illness onset. Therefore, we investigated the effects of 28-days of cannabis abstinence on psychotic and depressive symptomatology in cannabis dependent patients with schizophrenia. Males with cannabis dependence and co-morbid schizophrenia (n=19) and non-psychiatric controls (n=20) underwent 28-days of monitored cannabis abstinence. Clinical symptoms were assessed at baseline and then weekly. Abstinence was encouraged using weekly therapy sessions and contingency reinforcement, confirmed by twice-weekly urine assays. Forty-two percent (8/19) of patients and 55% (11/20) of controls achieved 28-days of sustained cannabis abstinence. In patients, PANSS subscores did not change over time irrespective of abstinence status. In contrast, patient abstainers demonstrated a more pronounced reduction in depression scores compared to non-abstainers, however, the Abstinence Status x Time interaction was non-significant. Short-term (28-days) cannabis abstinence is not associated with improvement in psychotic symptoms, but may be associated with improvement in depressive symptomatology in patients with schizophrenia. Future studies employing larger samples as well as a continuous cannabis-using group may help to better characterize the causal effects of cannabis on symptom outcomes in this disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

Cannabis and Ecstasy/ MDMA: empirical measures of creativity in recreational users.

PubMed

Jones, Katy A; Blagrove, M; Parrott, A C

2009-12-01

This study investigated the associations between chronic cannabis and Ecstasy/MDMA use and one objective and two subjective measure of creativity. Fifteen abstinent Ecstasy users, 15 abstinent cannabis users, and 15 nondrug-user controls, completed three measures of creativity: the Consequences behavioral test of creativity, self-assessed performance on the Consequences test, and Gough's Trait Self-Report Creative Adjective Checklist. The Consequences test involved five scenarios where possible consequences had to be devised; scoring was conducted by the standard blind rating (by two independent judges) for "remoteness" and "rarity," and by a frequency and rarity of responses method. Cannabis users had significantly more "rare-creative" responses than controls (Tukey, p < 0.05); this effect remained significant with gender as a covariate. There were no significant differences between the groups on the number of standard scoring "remote-creative" ideas or for fluency of responses. On self-rated creativity, there was a significant ANOVA group difference (p < 0.05), with Ecstasy users tending to rate their answers as more creative than controls (Tukey comparison; p = 0.058, two-tailed). Ecstasy users did not differ from controls on the behavioral measures of creativity, although there was a borderline trend for self-assessment of greater creativity. Cannabis users produced significantly more "rare-creative" responses, but did not rate themselves as more creative.

Residual neuropsychologic effects of cannabis.

PubMed

Pope, H G; Gruber, A J; Yurgelun-Todd, D

2001-12-01

Acute intoxication with cannabis clearly produces cognitive impairment, but it is less clear how long cognitive deficits persist after an individual stops regular cannabis use. Numerous methodologic difficulties confront investigators in the field attempting to assess the residual neuropsychologic effects of cannabis among heavy users, and these must be understood to properly evaluate available studies. At present, it appears safe to conclude that deficits in attention and memory persist for at least several days after discontinuing regular heavy cannabis use. Some of these deficits may be caused or exacerbated by withdrawal effects from the abrupt discontinuation of cannabis; these effects typically peak after 3 to 7 days of abstinence. It is less clear, however, whether heavy cannabis use can cause neurotoxicity that persists long after discontinuation of use. It seems likely that such long-term effects, if they exist, are subtle and not clinically disabling--at least in the majority of cases.

Neural correlates of performance monitoring in chronic cannabis users and cannabis-naïve controls

PubMed Central

Fridberg, Daniel J; Skosnik, Patrick D; Hetrick, William P; O’Donnell, Brian F

2014-01-01

Chronic cannabis use is associated with residual negative effects on measures of executive functioning. However, little previous work has focused specifically on executive processes involved in performance monitoring in frequent cannabis users. The present study investigated event-related potential (ERP) correlates of performance monitoring in chronic cannabis users. The error-related negativity (ERN) and error positivity (Pe), ERPs sensitive to performance monitoring, were recorded from 30 frequent cannabis users (mean usage=5.52 days/week) and 32 cannabis-naïve control participants during a speeded stimulus discrimination task. The “oddball” P3 ERP was recorded as well. Users and controls did not differ on the amplitude or latency of the ERN; however, Pe amplitude was larger among users. Users also showed increased amplitude and reduced latency of the P3 in response to infrequent stimuli presented during the task. Among users, urinary cannabinoid metabolite levels at testing were unrelated to ERP outcomes. However, total years of cannabis use correlated negatively with P3 latency and positively with P3 amplitude, and age of first cannabis use correlated negatively with P3 amplitude. The results of this study suggest that chronic cannabis use is associated with alterations in neural activity related to the processing of motivationally-relevant stimuli (P3) and errors (Pe). PMID:23427191

Low-dose vaporized cannabis significantly improves neuropathic pain.

PubMed

Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-02-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

Abnormal Medial Prefrontal Cortex Activity in Heavy Cannabis Users During Conscious Emotional Evaluation

PubMed Central

Lile, Joshua A.; Hanlon, Colleen A.; Porrino, Linda J.

2015-01-01

Rationale Long-term heavy cannabis users (cannabis users) who are not acutely intoxicated have diminished subconscious neural responsiveness to affective stimuli. Objective This study sought to determine if abnormal processing extends to the conscious evaluation of emotional stimuli. Methods Functional Magnetic Resonance Imaging (fMRI) was used to examine brain activity as cannabis users (N=16) and non-cannabis using controls (N=17) evaluated and categorized standardized International Affective Picture System (IAPS) stimuli. Individual judgments were used to isolate activity during the evaluation of emotional (i.e., emotional evaluation) or neutral (i.e., neutral evaluation) stimuli. Within- and between-group analyses were performed. Results Both groups judged the same stimuli as emotional and had activations in visual, midbrain, and middle cingulate cortices during emotional evaluation, relative to neutral. Within-group analyses also revealed amygdalar and inferior frontal gyrus activations in controls, but not cannabis users, and medial prefrontal cortex (mPFC) deactivations in cannabis users, but not controls, during emotional evaluation, relative to neutral. Between-group comparisons found that mPFC activity during positive and negative evaluation was significantly hypoactive in cannabis users, relative to controls. Conclusions Abnormal neural processing of affective content extends to the level of consciousness in cannabis users. The hypoactive mPFC responses observed resembles the attenuated mPFC responses found during increased non-affective cognitive load in prior research. These findings suggest that abnormal mPFC singling in cannabis users during emotional evaluation might be associated with increased non-affective cognitive load. PMID:26690589

Sex differences in cannabis withdrawal symptoms among treatment-seeking cannabis users.

PubMed

Herrmann, Evan S; Weerts, Elise M; Vandrey, Ryan

2015-12-01

Over 300,000 individuals enter treatment for cannabis-use disorders (CUDs) in the United States annually. Cannabis withdrawal is associated with poor CUD-treatment outcomes, but no prior studies have examined sex differences in withdrawal among treatment-seeking cannabis users. Treatment-seeking cannabis users (45 women and 91 men) completed a Marijuana Withdrawal Checklist (Budney, Novy, & Hughes, 1999, Budney, Moore, Vandrey, & Hughes, 2003) at treatment intake to retrospectively characterize withdrawal symptoms experienced during their most recent quit attempt. Scores from the 14-item Composite Withdrawal Discomfort Scale (WDS), a subset of the Marijuana Withdrawal Checklist that corresponds to valid cannabis withdrawal symptoms described in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; APA, 2013) were calculated. Demographic and substance-use characteristics, overall WDS scores, and scores on individual WDS symptoms were compared between women and men. Women had higher overall WDS scores than men, and women had higher scores than men on 6 individual symptoms in 2 domains, mood symptoms (i.e., irritability, restlessness, increased anger, violent outbursts), and gastrointestinal symptoms (i.e., nausea, stomach pain). Follow-up analyses isolating the incidence and severity of WDS symptoms demonstrated that women generally reported a higher number of individual withdrawal symptoms than men, and that they reported experiencing some symptoms as more severe. This is the first report to demonstrate that women seeking treatment for CUDs may experience more withdrawal then men during quit attempts. Prospective studies of sex differences in cannabis withdrawal are warranted. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

[Motivations for cannabis cessation, coping and adaptation strategies, and perceived benefits: impact on cannabis use relapse and abstinence].

PubMed

Chauchard, E; Septfons, A; Chabrol, H

2013-12-01

While cannabis has been recognized as the most illicit drug use in the world, few studies focusing on cannabis self-change and cannabis relapse or abstinence in adult non-treatment samples have been conducted. The first aim of this study was to understand cannabis self-change motives, coping and adaptation strategies and evaluating perceived benefits from cannabis cessation. The second aim was to compare, in a convenience sample of non-treatment-seeking adult cannabis smokers, motivations to quit smoking cannabis, coping and adaptive strategies, as well as perceived benefit from cessation between cannabis abstinent and participants who relapse. Sixty-three participants (31 men and 32 women) who attempted to quit cannabis in a non-controlled environment without medical help and were enrolled. They completed the Marijuana Quit Questionnaire (MJQQ), a self-report questionnaire collecting information in three areas: sociodemographic characteristics, cannabis use history (including any associated problems), and participants' characteristics regarding their "most difficult" (self-defined) attempt to quit in a non-controlled environment. For this study the index quit attempt was characterized in two areas: reasons for quitting marijuana, coping strategies used while quitting. Two additional questionnaires were added to the MJQQ; the Brief Cope, and a questionnaire assessing perceived benefit of the cannabis quit attempt. The participants were on average 28.5 years old (±5.1), and started using cannabis on average at 15.8 years (±2.8). Seventy-four percent (n=45) of the participants met the DSM-IV criteria for cannabis dependence before cannabis cessation. T-tests were used to compare abstainers and participants who relapsed after the quit attempt. Realizing that cannabis induces disabling cognitive disorders such as affection of memory, concentration and attention were reported by 71% of the participant as a motivation for quitting cannabis use. Then, being more

Association between cannabis use and treatment outcomes in patients receiving methadone maintenance treatment: a systematic review protocol.

PubMed

Zielinski, Laura; Bhatt, Meha; Eisen, Rebecca B; Perera, Stefan; Bhatnagar, Neera; MacKillop, James; Steiner, Meir; McDermid Vaz, Stephanie; Thabane, Lehana; Samaan, Zainab

2016-08-16

With the non-medical use of prescription opioids increasingly becoming a method of abuse in Canada, the number of patients requiring methadone maintenance treatment (MMT) for opioid use disorder has increased dramatically. The rate of cannabis use in this population is disproportionately high (~50 %). Because its use is generally perceived as harmless, cannabis use is often not monitored during MMT. Current literature regarding the effects of cannabis use on MMT is conflicting, and the presence and nature of an association has not been clearly established. The primary objective of this review will be to conduct a systematic review of the literature and, if appropriate, a meta-analysis to determine whether there is an association between cannabis use and MMT outcomes. A secondary objective will be to perform subgroup analyses (by age, sex, method of cannabis measurement, and country) to determine whether cannabis use differentially influences MMT outcomes within these subgroups. The search will be conducted on the following electronic databases using a predefined search strategy: MEDLINE, EMBASE, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Two authors (LZ and MB) will independently screen articles using predetermined inclusion/exclusion criteria and will extract data from included articles using a pilot-tested data extraction form. Disagreements at all stages of the screening process will be settled through discussion, and when consensus cannot be reached, a third author (ZS) will be consulted. An assessment of quality and risk of bias will be conducted on all included articles, and a sensitivity analysis will be used to compare results of studies with high and low risk of bias. We will perform random- and fixed-effects meta-analyses, if appropriate, with heterogeneity calculated using the I (2) statistic and formal evaluation of publication bias. Results of this systematic review will elucidate the association between cannabis

Quantification of Cannabinoid Content in Cannabis

NASA Astrophysics Data System (ADS)

Tian, Y.; Zhang, F.; Jia, K.; Wen, M.; Yuan, Ch.

2015-09-01

Cannabis is an economically important plant that is used in many fields, in addition to being the most commonly consumed illicit drug worldwide. Monitoring the spatial distribution of cannabis cultivation and judging whether it is drug- or fiber-type cannabis is critical for governments and international communities to understand the scale of the illegal drug trade. The aim of this study was to investigate whether the cannabinoids content in cannabis could be spectrally quantified using a spectrometer and to identify the optimal wavebands for quantifying the cannabinoid content. Spectral reflectance data of dried cannabis leaf samples and the cannabis canopy were measured in the laboratory and in the field, respectively. Correlation analysis and the stepwise multivariate regression method were used to select the optimal wavebands for cannabinoid content quantification based on the laboratory-measured spectral data. The results indicated that the delta-9-tetrahydrocannabinol (THC) content in cannabis leaves could be quantified using laboratory-measured spectral reflectance data and that the 695 nm band is the optimal band for THC content quantification. This study provides prerequisite information for designing spectral equipment to enable immediate quantification of THC content in cannabis and to discriminate drug- from fiber-type cannabis based on THC content quantification in the field.

Medical cannabis and chronic opioid therapy.

PubMed

Reisfield, Gary M

2010-12-01

Fourteen states and the District of Columbia have legalized the use of cannabis for medical purposes. A small, high-quality literature supports the efficacy of medical cannabis for the treatment of neuropathic pain. The smoked botanical product, however, is associated with a number of adverse medical and psychiatric consequences. Furthermore, experimental data indicate that acute use of cannabis results in impairment of every important metric related to the safe operation of a motor vehicle. Epidemiological data show associations between recent cannabis use and both psychomotor impairment and motor vehicle crashes, associations that are strengthened by the concomitant use of alcohol and other central nervous system depressants. Finally, data from pain clinics reveals an unusually high prevalence of cannabis use in nearly all age groups and an association between cannabis use and opioid and other substance misuse. Based on available data and expert opinion, concomitant use of cannabis and opioids is an absolute contraindication to the operation of a motor vehicle. In patients who use cannabis and are prescribed opioids, heightened vigilance for opioid- and other substance-related problems is warranted. It is appropriate to refrain from prescribing opioids to individuals using medical cannabis if there is reasonable suspicion that the combination will pose a risk to the patient or others.

Past year cannabis use and problematic cannabis use among adults by ethnicity in Ontario.

PubMed

Tuck, Andrew; Hamilton, Hayley A; Agic, Branka; Ialomiteanu, Anca R; Mann, Robert E

2017-10-01

Rates of cannabis use differ around the world; in Ontario, the rate of use has been stable since about 2005. Understanding which population groups are at greater risk for problematic cannabis use can help reduce long-term health effects and service expenses. The aim of this study was to explore differences in cannabis use among Canadian adults of different ethnic origins living in Ontario. Data are based on telephone interviews with 11,560 respondents and are derived from multiple cycles (2005-2011) of the Centre for Addiction and Mental Health's (CAMH) Monitor survey, an ongoing cross-sectional survey of adults in Ontario, Canada, aged 18 years and older. Data were analyzed using bivariate cross-tabulations and logistic regression. Problematic cannabis use was determined with a score of 8+ on the ASSIST-CIS to identify moderate/high problematic users. Lifetime, past year and problematic cannabis use (in the past 3 months) occurs among all ethnic groups: Canadian, East Asian, South East Asian, South Asian, Caribbean, African, East European, South European, North European, and Central West European. When compared to the Canadian group the odds of past year cannabis use was significantly lower for East Asians and South Asians, but higher for the Caribbean group. Significantly higher odds of problematic cannabis use were found for Caribbeans and Northern Europeans compared to Canadians. These results of this study provide an important basis for considering the possible impact of the impending legalization of cannabis in Canada among different ethnic groups. Copyright © 2017 Elsevier B.V. All rights reserved.

Cannabis use in people with Parkinson's disease and Multiple Sclerosis: A web-based investigation.

PubMed

Kindred, John H; Li, Kaigang; Ketelhut, Nathaniel B; Proessl, Felix; Fling, Brett W; Honce, Justin M; Shaffer, William R; Rudroff, Thorsten

2017-08-01

Cannabis has been used for medicinal purpose for thousands of years; however the positive and negative effects of cannabis use in Parkinson's disease (PD) and Multiple Sclerosis (MS) are mostly unknown. Our aim was to assess cannabis use in PD and MS and compare results of self-reported assessments of neurological disability between current cannabis users and non-users. An anonymous web-based survey was hosted on the Michael J. Fox Foundation and the National Multiple Sclerosis Society webpages from 15 February to 15 October 2016. The survey collected demographic and cannabis use information, and used standardized questionnaires to assess neurological function, fatigue, balance, and physical activity participation. Analysis of variance and chi-square tests were used for the analysis. The survey was viewed 801 times, and 595 participants were in the final data set. Seventy-six percent and 24% of the respondents reported PD and MS respectively. Current users reported high efficacy of cannabis, 6.4 (SD 1.8) on a scale from 0 to 7 and 59% reported reducing prescription medication since beginning cannabis use. Current cannabis users were younger and less likely to be classified as obese (P < 0.035). Cannabis users reported lower levels of disability, specifically in domains of mood, memory, and fatigue (P<0.040). Cannabis may have positive impacts on mood, memory, fatigue, and obesity status in people with PD and MS. Further studies using clinically and longitudinally assessed measurements of these domains are needed to establish if these associations are causal and determine the long-term benefits and consequences of cannabis use in people with PD and MS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Approach to cannabis use disorder in primary care

PubMed Central

Turner, Suzanne D.; Spithoff, Sheryl; Kahan, Meldon

2014-01-01

Objective To review the clinical features and complications of at-risk cannabis use and cannabis use disorder, and to outline an office-based protocol for screening, identifying, and managing this disorder. Sources of information PubMed was searched for controlled trials, observational studies, and reviews on cannabis use among adolescents and young adults; cannabis-related medical and psychiatric harms; cannabis use disorder and its treatment; and lower-risk cannabis use guidelines. Main message Physicians should ask all patients about cannabis use. They should ask adolescents and young adults and those at highest risk of cannabis-related harms (those with concurrent psychiatric or substance use disorders) more frequently. Physicians should also ask about cannabis use in patients who have problems that could be caused by cannabis, such as mood disorders, psychosis, and respiratory symptoms. In patients who report cannabis use, physicians should inquire about frequency and amount, tolerance and withdrawal symptoms, attempts to reduce use, and cannabis-related harms. Lower-risk cannabis users smoke, inhale, or ingest cannabis occasionally without evidence of school, work, or social dysfunction; those with problematic use often use cannabis daily or almost daily, have difficulty reducing their use, and have impaired school, work, or social functioning. Physicians should offer all patients with problematic use brief advice and counseling, focusing on the health effects of cannabis and setting a goal of abstinence (some higher-risk groups should not use cannabis at all) or reduced use, and they should provide practical strategies to reduce cannabis use. Physicians should incorporate simple motivational interviewing techniques into the counseling sessions. They should refer those patients who are unable to reduce use or who are experiencing harms from cannabis use to specialized care, while ensuring those patients remain connected to primary care. As well, physicians

Cannabis-Induced Acute Pancreatitis: A Systematic Review.

PubMed

Barkin, Jodie A; Nemeth, Zsuzsanna; Saluja, Ashok K; Barkin, Jamie S

2017-09-01

Cannabis is the most frequently consumed illicit drug in the world, with higher prevalence under the age of 35 years. Cannabis was first reported as a possible cause of acute pancreatitis (AP) in 2004. The aim of this systematic review is to examine cannabis use as an etiology of AP. A search using PubMed/Medline, Embase, Scopus, and Cochrane was performed without language or year limitations to May 1, 2016. Search terms were "Cannabis" and "Acute Pancreatitis" with all permutations. The search yielded 239 results. Acute pancreatitis was defined by meeting 2 of 3 Revised Atlanta Classification criteria. Cannabis-induced AP was defined by preceding use of cannabis and exclusion of common causes of AP when reported. Sixteen papers met inclusion criteria dating from 2004 to 2016. There were 26 cases of cannabis-induced AP (23/26 men; 24/26 under the age of 35 y). Acute pancreatitis correlated with increased cannabis use in 18 patients. Recurrent AP related temporally to cannabis use was reported in 15 of 26. There are 13 reports of no further AP episodes after cannabis cessation. Cannabis is a possible risk factor for AP and recurrent AP, occurring primarily in young patients under the age of 35 years. Toxicology screens should be considered in all patients with idiopathic AP.

Daily Use, Especially of High-Potency Cannabis, Drives the Earlier Onset of Psychosis in Cannabis Users

PubMed Central

Di Forti, Marta; Sallis, Hannah; Allegri, Fabio; Trotta, Antonella; Ferraro, Laura; Stilo, Simona A.; Marconi, Arianna; La Cascia, Caterina; Reis Marques, Tiago; Pariante, Carmine; Dazzan, Paola; Mondelli, Valeria; Paparelli, Alessandra; Kolliakou, Anna; Prata, Diana; Gaughran, Fiona; David, Anthony S.; Morgan, Craig; Stahl, Daniel; Khondoker, Mizanur; MacCabe, James H.; Murray, Robin M.

2014-01-01

Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. Methods: We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. Results: Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16–1.74; P < .001). This association remained significant after controlling for gender (HR = 1.39; 95% CI: 1.11–1.68; P < .001). Those who had started cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06–1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P < .0001); these daily users of high-potency cannabis had an onset an average of 6 years earlier than that of non-cannabis users. Conclusions: Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users. PMID:24345517

Relation between cannabis use and subcortical volumes in people at clinical high risk of psychosis

PubMed Central

Buchy, Lisa; Mathalon, Daniel H.; Cannon, Tyrone D.; Cadenhead, Kristin S.; Cornblatt, Barbara A.; McGlashan, Thomas H.; Perkins, Diana O.; Seidman, Larry J.; Tsuang, Ming T.; Walker, Elaine F.; Woods, Scott W.; Bearden, Carrie E.; Addington, Jean

2016-01-01

Among people at genetic risk of schizophrenia, those who use cannabis show smaller thalamic and hippocampal volumes. We evaluated this relationship in people at clinical high risk (CHR) of psychosis. The Alcohol and Drug Use Scale was used to identify 132 CHR cannabis users, the majority of whom were non-dependent cannabis users, 387 CHR non-users, and 204 healthy control non-users, and all participants completed magnetic resonance imaging scans. Volumes of the thalamus, hippocampus and amygdala were extracted with FreeSurfer, and compared across groups. Comparing all CHR participants with healthy control participants revealed no significant differences in volumes of any ROI. However, when comparing CHR users to CHR non-users, a significant ROI × Cannabis group effect emerged: CHR users showed significantly smaller amygdala compared to CHR non-users. However, when limiting analysis to CHR subjects who reported using alcohol at a ‘use without impairment’ severity level, the amygdala effect was non-significant; rather, smaller hippocampal volumes were seen in CHR cannabis users compared to non-users. Controlling statistically for effects of alcohol and tobacco use rendered all results non-significant. These results highlight the importance of controlling for residual confounding effects of other substance use when examining the relationship between cannabis use and neural structure. PMID:27289213

[Somatic consequences of cannabis use].

PubMed

Cottencin, Olivier; Bence, Camille; Rolland, Benjamin; Karila, Laurent

2013-12-01

Cannabis can have negative effects in its users, and a range of acute and chronic health problems associated with cannabis use has been dentified. Acute cannabis consumption is rarely lethal but it is associated with an increased risk of motor vehicle accident because of longer reaction time or impaired motor coordination. Chronic effects of cannabis use include generally cardiovascular and respiratory consequences but there are also oral, gastrointestinal, cutaneous and mucous, metabolic, gynecologic and obstetrical, sexual consequences, and cancer But associated tobacco smoking or other potential confounders may explain part of those somatic consequences.

Cannabis use in adolescents: the impact of risk and protective factors and social functioning.

PubMed

Best, David; Gross, Samantha; Manning, Victoria; Gossop, Michael; Witton, John; Strang, John

2005-11-01

The study uses a school-based sample to test the social and familial risk and protective factors relating to cannabis use. Based on a self-completion survey of 2078 14-16-year-olds (mean age of 15 years) attending seven standard state-run secondary schools in south London, an assessment was made of rates and risk factors for cannabis use. Twenty-four per cent of the total sample had ever used cannabis, with 15% having done so in the month prior to assessment. In addition to greater likelihood of illicit drug use, lifetime cannabis users were less likely to spend time regularly with both their mothers and fathers, but more likely to spend free time with friends who smoked, drank alcohol and used illicit drugs, and with friends involved in criminal activities. Among those who had ever used cannabis, frequency of cannabis use was predicted (using linear regression) by two onset factors (earlier initiation of drinking and cannabis use were both linked to more frequent use) and two social factors (more time spent with drug-using friends and less time spent with the mother). Overall, the study showed that early onset, itself predicted by social networks, is linked to more frequent use of cannabis and that this appears to be sustained by less time spent with parents and more with drug-using peers.

Rapid elimination of Carboxy-THC in a cohort of chronic cannabis users.

PubMed

Lewis, John; Molnar, Anna; Allsop, David; Copeland, Jan; Fu, Shanlin

2016-01-01

Urinary 11-nor-Δ(9)-tetrahydrocannabinol-9-carboxylic acid (Carboxy-THC) concentrations, normalised to creatinine output, have been demonstrated to be a useful tool in the interpretation of the results of a series of urine tests for cannabis. These tests, often termed historical data, can be used to identify potential chronic cannabis users who may present occupational health and safety risks within the workplace. Conversely, the data can also be used to support employee claims of previous regular, rather than recent, cannabis use. This study aimed at examining the mean elimination of Carboxy-THC in 37 chronic users undergoing voluntary abstinence over a 2-week period. Urine specimens were collected prior to the study and after 1 and 2 weeks of abstinence. Carboxy-THC levels in urine were measured by gas chromatography-mass spectrometry (GC-MS) following alkaline hydrolysis, organic solvent extraction and derivatisation to form its pentafluoropropionic derivative. The creatinine-normalised Carboxy-THC concentrations declined rapidly over the 2 weeks of abstinence period and the majority of chronic cannabis users (73%) reduced their urinary Carboxy-THC levels to below the 15-μg/L confirmatory cutoff within that time. The study further highlights the value of historical urinary Carboxy-THC data as a means of identifying potential occupational health and safety risks among chronic cannabis users.

[Cognitive abnormalities and cannabis use].

PubMed

Solowij, Nadia; Pesa, Nicole

2010-05-01

Evidence that cannabis use impairs cognitive function in humans has been accumulating in recent decades. The purpose of this overview is to update knowledge in this area with new findings from the most recent literature. Literature searches were conducted using the Web of Science database up to February 2010. The terms searched were: "cannabi*" or "marijuana", and "cogniti*" or "memory" or "attention" or "executive function", and human studies were reviewed preferentially over the animal literature. Cannabis use impairs memory, attention, inhibitory control, executive functions and decision making, both during the period of acute intoxication and beyond, persisting for hours, days, weeks or more after the last use of cannabis. Pharmacological challenge studies in humans are elucidating the nature and neural substrates of cognitive changes associated with various cannabinoids. Long-term or heavy cannabis use appears to result in longer-lasting cognitive abnormalities and possibly structural brain alterations. Greater adverse cognitive effects are associated with cannabis use commencing in early adolescence. The endogenous cannabinoid system is involved in regulatory neural mechanisms that modulate processes underlying a range of cognitive functions that are impaired by cannabis. Deficits in human users most likely therefore reflect neuroadaptations and altered functioning of the endogenous cannabinoid system.

Cannabis and Cannabinoids for Chronic Pain.

PubMed

Romero-Sandoval, E Alfonso; Kolano, Ashley L; Alvarado-Vázquez, P Abigail

2017-10-05

The purpose of this study was to provide the most up-to-date scientific evidence of the potential analgesic effects, or lack thereof, of the marijuana plant (cannabis) or cannabinoids, and of safety or tolerability of their long-term use. We found that inhaled (smoked or vaporized) cannabis is consistently effective in reducing chronic non-cancer pain. Oral cannabinoids seem to improve some aspects of chronic pain (sleep and general quality of life), or cancer chronic pain, but they do not seem effective in acute postoperative pain, abdominal chronic pain, or rheumatoid pain. The available literature shows that inhaled cannabis seems to be more tolerable and predictable than oral cannabinoids. Cannabis or cannabinoids are not universally effective for pain. Continued research on cannabis constituents and improving bioavailability for oral cannabinoids is needed. Other aspects of pain management in patients using cannabis require further open discussion: concomitant opioid use, medical vs. recreational cannabis, abuse potential, etc.

Effects of quitting cannabis on respiratory symptoms.

PubMed

Hancox, Robert J; Shin, Hayden H; Gray, Andrew R; Poulton, Richie; Sears, Malcolm R

2015-07-01

Smoking cannabis is associated with symptoms of bronchitis. Little is known about the persistence of symptoms after stopping cannabis use. We assessed associations between changes in cannabis use and respiratory symptoms in a population-based cohort of 1037 young adults. Participants were asked about cannabis and tobacco use at ages 18, 21, 26, 32 and 38 years. Symptoms of morning cough, sputum production, wheeze, dyspnoea on exertion and asthma diagnoses were ascertained at the same ages. Frequent cannabis use was defined as ≥52 occasions over the previous year. Associations between frequent cannabis use and respiratory symptoms were analysed using generalised estimating equations with adjustments for tobacco smoking, asthma, sex and age. Frequent cannabis use was associated with morning cough (OR 1.97, p<0.001), sputum production (OR 2.31, p<0.001) and wheeze (OR 1.55, p<0.001). Reducing or quitting cannabis use was associated with reductions in the prevalence of cough, sputum and wheeze to levels similar to nonusers.Frequent cannabis use is associated with symptoms of bronchitis in young adults. Reducing cannabis use often leads to a resolution of these symptoms. Copyright ©ERS 2015.

Effects of quitting cannabis on respiratory symptoms

PubMed Central

Hancox, Robert J.; Shin, Hayden H.; Gray, Andrew R.; Poulton, Richie; Sears, Malcolm R.

2016-01-01

Smoking cannabis is associated with symptoms of bronchitis. Little is known about the persistence of symptoms after stopping cannabis use. We assessed associations between changes in cannabis use and respiratory symptoms in a population-based cohort of 1037 young adults. Participants were asked about cannabis and tobacco use at ages 18, 21, 26, 32 and 38 years. Symptoms of morning cough, sputum production, wheeze, dyspnoea on exertion and asthma diagnoses were ascertained at the same ages. Frequent cannabis use was defined as ≥52 occasions over the previous year. Associations between frequent cannabis use and respiratory symptoms were analysed using generalised estimating equations with adjustments for tobacco smoking, asthma, sex and age. Frequent cannabis use was associated with morning cough (OR 1.97, p<0.001), sputum production (OR 2.31, p<0.001) and wheeze (OR 1.55, p<0.001). Reducing or quitting cannabis use was associated with reductions in the prevalence of cough, sputum and wheeze to levels similar to nonusers. Frequent cannabis use is associated with symptoms of bronchitis in young adults. Reducing cannabis use often leads to a resolution of these symptoms. PMID:25837035

Medicinal cannabis (Bedrolite) substitution therapy in inpatients with a psychotic disorder and a comorbid cannabis use disorder: A case series.

PubMed

Schipper, Regi; Dekker, Mathilde; de Haan, Lieuwe; van den Brink, Wim

2018-03-01

Cannabis use disorders are frequently comorbid in patients with a psychotic disorder and are associated with worse outcomes. To date there are no proven effective strategies to achieve cannabis abstinence in this population. An alternative for abstinence might be harm reduction, i.e. replacing the use of street cannabis with high tetrahydrocannabinol and low cannabidiol levels by medicinal cannabis variants with relatively low tetrahydrocannabinol and relatively high cannabidiol levels, thereby reducing the psychosis inducing effects of cannabis and enhancing the antipsychotic effects of cannabis. Here we present the data of a case series with seven inpatients diagnosed with a psychotic disorder and a treatment-resistant cannabis use disorder who received substitution therapy with a low tetrahydrocannabinol medicinal cannabis variant (Bedrolite). The results suggest that the low tetrahydrocannabinol medicinal cannabis variant Bedrolite is not effective in the treatment of inpatients with a psychotic disorder and comorbid cannabis use disorder. Bedrolite is thus not very likely to become an effective harm reduction strategy in these patients.

Cannabis withdrawal is common among treatment-seeking adolescents with cannabis dependence and major depression, and is associated with rapid relapse to dependence.

PubMed

Cornelius, Jack R; Chung, Tammy; Martin, Christopher; Wood, D Scott; Clark, Duncan B

2008-11-01

Recently, reports have suggested that cannabis withdrawal occurs commonly in adults with cannabis dependence, though it is unclear whether this extends to those with comorbid depression or to comorbid adolescents. We hypothesized that cannabis withdrawal would be common among our sample of comorbid adolescents and young adults, and that the presence of cannabis withdrawal symptoms would be associated with a self-reported past history of rapid reinstatement of cannabis dependence symptoms (rapid relapse). The participants in this study included 170 adolescents and young adults, including 104 with cannabis dependence, 32 with cannabis abuse, and 34 with cannabis use without dependence or abuse. All of these subjects demonstrated current depressive symptoms and cannabis use, and most demonstrated current DSM-IV major depressive disorder and current comorbid cannabis dependence. These subjects had presented for treatment for either of two double-blind, placebo-controlled trials involving fluoxetine. Cannabis withdrawal was the most commonly reported cannabis dependence criterion among the 104 subjects in our sample with cannabis dependence, being noted in 92% of subjects, using a two-symptom cutoff for determination of cannabis withdrawal. The most common withdrawal symptoms among those with cannabis dependence were craving (82%), irritability (76%), restlessness (58%), anxiety (55%), and depression (52%). Cannabis withdrawal symptoms (in the N=170 sample) were reported to have been associated with rapid reinstatement of cannabis dependence symptoms (rapid relapse). These findings suggest that cannabis withdrawal should be included as a diagnosis in the upcoming DSM-V, and should be listed in the upcoming criteria list for the DSM-V diagnostic category of cannabis dependence.

Drug vaping applied to cannabis: Is "Cannavaping" a therapeutic alternative to marijuana?

PubMed

Varlet, Vincent; Concha-Lozano, Nicolas; Berthet, Aurélie; Plateel, Grégory; Favrat, Bernard; De Cesare, Mariangela; Lauer, Estelle; Augsburger, Marc; Thomas, Aurélien; Giroud, Christian

2016-05-26

Therapeutic cannabis administration is increasingly used in Western countries due to its positive role in several pathologies. Dronabinol or tetrahydrocannabinol (THC) pills, ethanolic cannabis tinctures, oromucosal sprays or table vaporizing devices are available but other cannabinoids forms can be used. Inspired by the illegal practice of dabbing of butane hashish oil (BHO), cannabinoids from cannabis were extracted with butane gas, and the resulting concentrate (BHO) was atomized with specific vaporizing devices. The efficiency of "cannavaping," defined as the "vaping" of liquid refills for e-cigarettes enriched with cannabinoids, including BHO, was studied as an alternative route of administration for therapeutic cannabinoids. The results showed that illegal cannavaping would be subjected to marginal development due to the poor solubility of BHO in commercial liquid refills (especially those with high glycerin content). This prevents the manufacture of liquid refills with high BHO concentrations adopted by most recreational users of cannabis to feel the psychoactive effects more rapidly and extensively. Conversely, "therapeutic cannavaping" could be an efficient route for cannabinoids administration because less concentrated cannabinoids-enriched liquid refills are required. However, the electronic device marketed for therapeutic cannavaping should be carefully designed to minimize potential overheating and contaminant generation.

An exploratory study of cannabis withdrawal among Indigenous Australian prison inmates: study protocol.

PubMed

Rogerson, Bernadette; Copeland, Jan; Buttner, Petra; Bohanna, India; Cadet-James, Yvonne; Sarnyai, Zoltan; Clough, Alan R

2013-05-28

Cannabis use and dependence is a serious health and criminal justice issue among incarcerated populations internationally. Upon abrupt, enforced cessation of cannabis, prisoners may suffer irritability and anger that can lead to threatening behaviour, intimidation, violence, sleep disturbances and self-harm. Cannabis withdrawal syndrome, proposed for inclusion in the Diagnostic and Statistical Manual of Mental Disorders in 2013, has not been examined in Indigenous populations. Owing to the exceptionally high rates of cannabis use in the community, high proportions of Australian Indigenous prisoners may suffer from withdrawal upon entry to custody. 60 male and 60 female Indigenous prisoners (18-40 years) at a high risk of cannabis dependence will be recruited upon entry to custody. A pictorial representation of the standard Cannabis Withdrawal Scale will be tested for reliability and validity. Cortisol markers will be measured in saliva, as the indicators of onset and severity of cannabis withdrawal and psychological distress. The characteristics will be described as percentages and mean or median values with 95% CI. Receiver operator curve analysis will determine an ideal cut-off of the Cannabis Withdrawal Scale and generalised estimating equations modelling will test changes over time. The acceptability and efficacy of proposed resources will be assessed qualitatively using thematic analysis. A valid and reliable measure of cannabis withdrawal for use with Indigenous populations, the onset and time course of withdrawal symptoms in this population and the development of culturally acceptable resources and interventions to identify and manage cannabis withdrawal. The project has been approved by the James Cook University Human Research Ethics Committee (approval number H4651).The results will be reported via peer reviewed publications, conference, seminar presentations and on-line media for national and international dissemination.

Sex-dependent effects of cannabis-induced analgesia.

PubMed

Cooper, Ziva D; Haney, Margaret

2016-10-01

Preclinical studies demonstrate that cannabinoid-mediated antinociceptive effects vary according to sex; it is unknown if these findings extend to humans. This retrospective analysis compared the analgesic, subjective and physiological effects of active cannabis (3.56-5.60% THC) and inactive cannabis (0.00% THC) in male (N=21) and female (N=21) cannabis smokers under double-blind, placebo-controlled conditions. Pain response was measured using the Cold-Pressor Test (CPT). Participants immersed their hand in cold water (4°C); times to report pain (pain sensitivity) and withdraw the hand (pain tolerance) were recorded. Subjective drug ratings were also measured. Among men, active cannabis significantly decreased pain sensitivity relative to inactive cannabis (p<0.01). In women, active cannabis failed to decrease pain sensitivity relative to inactive. Active cannabis increased pain tolerance in both men women immediately after smoking (p<0.001); a trend was observed for differences between men and women (p<0.10). Active cannabis also increased subjective ratings of cannabis associated with abuse liability ('Take again,' 'Liking,' 'Good drug effect'), drug strength, and 'High' relative to inactive in both men and women (p<0.01). These results indicate that in cannabis smokers, men exhibit greater cannabis-induced analgesia relative to women. These sex-dependent differences are independent of cannabis-elicited subjective effects associated with abuse-liability, which were consistent between men and women. As such, sex-dependent differences in cannabis's analgesic effects are an important consideration that warrants further investigation when considering the potential therapeutic effects of cannabinoids for pain relief. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sex-Dependent Effects Of Cannabis-Induced Analgesia

PubMed Central

Cooper, Ziva D.; Haney, Margaret

2016-01-01

Background Preclinical studies demonstrate that cannabinoid-mediated antinociceptive effects vary according to sex; it is unknown if these findings extend to humans. Methods This retrospective analysis compared the analgesic, subjective and physiological effects of active cannabis (3.56 - 5.60% THC) and inactive cannabis (0.00% THC) in male (N = 21) and female (N = 21) cannabis smokers under double-blind, placebo-controlled conditions. Pain response was measured using the Cold-Pressor Test (CPT). Participants immersed their hand in cold water (4°C); times to report pain (pain sensitivity) and withdraw the hand (pain tolerance) were recorded. Subjective drug ratings were also measured. Results Among men, active cannabis significantly decreased pain sensitivity relative to inactive cannabis (p < 0.01). In women, active cannabis failed to decrease pain sensitivity relative to inactive. Active cannabis increased pain tolerance in both men women immediately after smoking (p < 0.001); a trend was observed for differences between men and women (p < 0.10). Active cannabis also increased subjective ratings of cannabis associated with abuse liability (‘Take again,’ ‘Liking,’ ‘Good drug effect’), drug strength, and ‘High’ relative to inactive in both men and women (p < 0.01). Conclusions These results indicate that in cannabis smokers, men exhibit greater cannabis-induced analgesia relative to women. These sex-dependent differences are independent of cannabis-elicited subjective effects associated with abuse-liability, which were consistent between men and women. As such, sex-dependent differences in cannabis's analgesic effects are an important consideration that warrants further investigation when considering the potential therapeutic effects of cannabinoids for pain relief. PMID:27522535

Quantifying the Clinical Significance of Cannabis Withdrawal

PubMed Central

Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

2012-01-01

Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

Medicinal cannabis: moving the debate forward.

PubMed

Newton-Howes, Giles; McBride, Sam

2016-11-18

There has been increased interest in cannabis as a medicine both nationally and internationally. Internationally, cannabis is accepted as a medication for a variety of purposes in a variety of legal guises and this, associated with anecdotes of the utility of cannabis as medication has led for calls for it to be 'medicalised' in New Zealand. This viewpoint discusses the issues associated with this approach to accessing cannabis and some of the difficulties that may be associated with it. It is important doctors are at the forefront of the debate surrounding medicalised cannabis. Recommendations as to the ongoing debate are offered.

Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.

PubMed

Di Forti, Marta; Sallis, Hannah; Allegri, Fabio; Trotta, Antonella; Ferraro, Laura; Stilo, Simona A; Marconi, Arianna; La Cascia, Caterina; Reis Marques, Tiago; Pariante, Carmine; Dazzan, Paola; Mondelli, Valeria; Paparelli, Alessandra; Kolliakou, Anna; Prata, Diana; Gaughran, Fiona; David, Anthony S; Morgan, Craig; Stahl, Daniel; Khondoker, Mizanur; MacCabe, James H; Murray, Robin M

2014-11-01

Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16-1.74; P < .001). This association remained significant after controlling for gender (HR = 1.39; 95% CI: 1.11-1.68; P < .001). Those who had started cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06-1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P < .0001); these daily users of high-potency cannabis had an onset an average of 6 years earlier than that of non-cannabis users. Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Limitations to the Dutch cannabis toleration policy: Assumptions underlying the reclassification of cannabis above 15% THC.

PubMed

Van Laar, Margriet; Van Der Pol, Peggy; Niesink, Raymond

2016-08-01

The Netherlands has seen an increase in Δ9-tetrahydrocannabinol (THC) concentrations from approximately 8% in the 1990s up to 20% in 2004. Increased cannabis potency may lead to higher THC-exposure and cannabis related harm. The Dutch government officially condones the sale of cannabis from so called 'coffee shops', and the Opium Act distinguishes cannabis as a Schedule II drug with 'acceptable risk' from other drugs with 'unacceptable risk' (Schedule I). Even in 1976, however, cannabis potency was taken into account by distinguishing hemp oil as a Schedule I drug. In 2011, an advisory committee recommended tightening up legislation, leading to a 2013 bill proposing the reclassification of high potency cannabis products with a THC content of 15% or more as a Schedule I drug. The purpose of this measure was twofold: to reduce public health risks and to reduce illegal cultivation and export of cannabis by increasing punishment. This paper focuses on the public health aspects and describes the (explicit and implicit) assumptions underlying this '15% THC measure', as well as to what extent these are supported by scientific research. Based on scientific literature and other sources of information, we conclude that the 15% measure can provide in theory a slight health benefit for specific groups of cannabis users (i.e., frequent users preferring strong cannabis, purchasing from coffee shops, using 'steady quantities' and not changing their smoking behaviour), but certainly not for all cannabis users. These gains should be weighed against the investment in enforcement and the risk of unintended (adverse) effects. Given the many assumptions and uncertainty about the nature and extent of the expected buying and smoking behaviour changes, the measure is a political choice and based on thin evidence. Copyright © 2016 Springer. Published by Elsevier B.V. All rights reserved.

Medicinal cannabis does not influence the clinical pharmacokinetics of irinotecan and docetaxel.

PubMed

Engels, Frederike K; de Jong, Floris A; Sparreboom, Alex; Mathot, Ron A A; Loos, Walter J; Kitzen, Jos J E M; de Bruijn, Peter; Verweij, Jaap; Mathijssen, Ron H J

2007-03-01

To date, data regarding the potential of cannabinoids to modulate cytochrome P450 isozyme 3A (CYP3A) activity are contradictory. Recently, a standardized medicinal cannabis product was introduced in The Netherlands. We anticipated an increased use of medicinal cannabis concurrent with anticancer drugs, and undertook a drug-interaction study to evaluate the effect of concomitant medicinal cannabis on the pharmacokinetics of irinotecan and docetaxel, both subject to CYP3A-mediated biotransformation. Twenty-four cancer patients were treated with i.v. irinotecan (600 mg, n = 12) or docetaxel (180 mg, n = 12), followed 3 weeks later by the same drugs concomitant with medicinal cannabis (200 ml herbal tea, 1 g/l) for 15 consecutive days, starting 12 days before the second treatment. Blood samples were obtained up to 55 hours after dosing and analyzed for irinotecan and its metabolites (SN-38, SN-38G), respectively, or docetaxel. Pharmacokinetic analyses were performed during both treatments. Results are reported as the mean ratio (95% confidence interval [CI]) of the observed pharmacokinetic parameters with and without concomitant medicinal cannabis. Medicinal cannabis administration did not significantly influence exposure to and clearance of irinotecan (1.04; CI, 0.96-1.11 and 0.97; CI, 0.90-1.05, respectively) or docetaxel (1.11; CI, 0.94-1.28 and 0.95; CI, 0.82-1.08, respectively). Coadministration of medicinal cannabis, as herbal tea, in cancer patients treated with irinotecan or docetaxel does not significantly influence the plasma pharmacokinetics of these drugs. The evaluated variety of medicinal cannabis can be administered concomitantly with both anticancer agents without dose adjustments.

Correlates of intentions to use cannabis among US high school seniors in the case of cannabis legalization.

PubMed

Palamar, Joseph J; Ompad, Danielle C; Petkova, Eva

2014-05-01

Support for cannabis ("marijuana") legalization is increasing in the United States (US). Use was recently legalized in two states and in Uruguay, and other states and countries are expected to follow suit. This study examined intentions to use among US high school seniors if cannabis were to become legally available. Data from the last five cohorts (2007-2011) of high school seniors in Monitoring the Future, an annual nationally representative survey of students in the US were utilized. Data were analyzed separately for the 6116 seniors who reported no lifetime use of cannabis and the 3829 seniors who reported lifetime use (weighted Ns). We examined whether demographic characteristics, substance use and perceived friend disapproval towards cannabis use were associated with (1) intention to try cannabis among non-lifetime users, and (2) intention to use cannabis as often or more often among lifetime users, if cannabis was legal to use. Ten percent of non-cannabis-using students reported intent to initiate use if legal and this would be consistent with a 5.6% absolute increase in lifetime prevalence of cannabis use in this age group from 45.6% (95% CI=44.6, 46.6) to 51.2% (95% CI=50.2, 52.2). Eighteen percent of lifetime users reported intent to use cannabis more often if it was legal. Odds for intention to use outcomes increased among groups already at high risk for use (e.g., males, whites, cigarette smokers) and odds were reduced when friends disapproved of use. However, large proportions of subgroups of students normally at low risk for use (e.g., non-cigarette-smokers, religious students, those with friends who disapprove of use) reported intention to use if legal. Recent use was also a risk factor for reporting intention to use as often or more often. Prevalence of cannabis use is expected to increase if cannabis is legal to use and legally available. Copyright © 2014 Elsevier B.V. All rights reserved.

Correlates of Intentions to Use Cannabis among US High School Seniors in the Case of Cannabis Legalization

PubMed Central

Palamar, Joseph J.; Ompad, Danielle C.; Petkova, Eva

2014-01-01

Background Support for cannabis (“marijuana”) legalization is increasing in the United States (US). Use was recently legalized in two states and in Uruguay, and other states and countries are expected to follow suit. This study examined intentions to use among US high school seniors if cannabis were to become legally available. Methods Data from the last five cohorts (2007–2011) of high school seniors in Monitoring the Future, an annual nationally representative survey of students in the US were utilized. Data were analyzed separately for the 6,116 seniors who reported no lifetime use of cannabis and the 3,828 seniors who reported lifetime use (weighted Ns). We examined whether demographic characteristics, substance use and perceived friend disapproval towards cannabis use were associated with 1) intention to try cannabis among non-lifetime users, and 2) intention to use cannabis as often or more often among lifetime users, if cannabis was legal to use. Results Ten percent of non-cannabis-using students reported intent to initiate use if legal and this would constitute a 5.6% absolute increase in lifetime prevalence of cannabis use in this age group from 45.6% (95% CI=46.6, 44.6) to 51.2% (95% CI=50.2, 52.2). Eighteen percent of lifetime users reported intent to use cannabis more often if it was legal. Odds for intention to use outcomes increased among groups already at high risk for use (e.g., males, whites, cigarette smokers) and odds were reduced when friends disapproved of use. However, large proportions of subgroups of students normally at low risk for use (e.g., non-cigarette-smokers, religious students, those with friends who disapprove of use) reported intention to use if legal. Recent use was also a risk factor for reporting intention to use as often or more often. Conclusion Prevalence of cannabis use is expected to increase if cannabis is legal to use and legally available. PMID:24589410

Baclofen in the management of cannabis dependence syndrome.

PubMed

Imbert, Bruce; Labrune, Nathalie; Lancon, Christophe; Simon, Nicolas

2014-02-01

Cannabis is the most commonly used illicit drug in the world. However, only few studies have shown the efficacy of pharmacologic agents in targeting cannabis withdrawal symptoms or reducing the reinforcing effects of cannabis. Baclofen has been shown to reduce cannabis withdrawal symptoms and the subjective effects of cannabis. We think that the clinical utility of baclofen for cannabis dependence is a reasonable approach. A case report using baclofen is presented and provides preliminary support for the use of baclofen in the management of cannabis dependence.

[Cannabis smoking and lung cancer].

PubMed

Underner, M; Urban, T; Perriot, J; de Chazeron, I; Meurice, J-C

2014-06-01

Cannabis is the most commonly smoked illicit substance in the world. It can be smoked alone in plant form (marijuana) but it is mainly smoked mixed with tobacco. The combined smoking of cannabis and tobacco is a common-place phenomenon in our society. However, its use is responsible for severe pulmonary consequences. The specific impact of smoking cannabis is difficult to assess precisely and to distinguish from the effect of tobacco. Marijuana smoke contains polycyclic aromatic hydrocarbons and carcinogens at higher concentration than tobacco smoke. Cellular, tissue, animal and human studies, and also epidemiological studies, show that marijuana smoke is a risk factor for lung cancer. Cannabis exposure doubles the risk of developing lung cancer. This should encourage clinicians to identify cannabis use and to offer patients support in quitting. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Transient Retinal Dysfunctions after Acute Cannabis Use.

PubMed

Schwitzer, Thomas; Robert, Matthieu P; Giersch, Anne; Angioi-Duprez, Karine; Ingster-Moati, Isabelle; Pon-Monnier, Amandine; Schwan, Raymund; Laprevote, Vincent

2016-01-01

Although cannabis is very widespread worldwide, the impact of cannabis on visual function remains poorly understood. This is partly due to numerous difficulties met in developing clinical studies in cannabis users. Here, we report the first documented case of neuroretinal dysfunction after acute cannabis smoking. This observation was favored by the need of an annual ophthalmic evaluation in the context of a chloroquine intake for a systemic lupus erythematosus in a 47-year-old heavy cannabis user. A complete ophthalmic evaluation including visual acuity tests, intraocular pressure, fundoscopic examination, automated 10° central visual field, full-field electroretinogram (ERG) and multifocal ERG was performed twice - 30 min and 5 h after cannabis smoking. A strong decrease (up to 48%) in the a-wave amplitude of the full-field ERG was measured 30 min after cannabis smoking for all scotopic responses compared with the responses 5 h after smoking. Other tests showed reproducible results between the 2 series of measurements. This clinical case suggests that acute inhalation of cannabis affects the photoreceptors functioning. This rare situation suggests further investigations are required on the impact of cannabis on retinal processing, especially since cannabis has been incriminated in car injuries. © 2016 S. Karger AG, Basel.

Quality of life and recreational cannabis use.

PubMed

Goldenberg, Matthew; IsHak, Waguih William; Danovitch, Itai

2017-01-01

Cannabis is now the most commonly used illicit drug in the United States and use is increasing. Frequent cannabis use has been associated with adverse social and health effects. We sought to evaluate the relationship between recreational cannabis use and Quality of Life (QoL), a person-centered measure that characterizes the overall sense of health and wellbeing. We hypothesized that QoL would be unchanged or increased among recreational cannabis users, who did not meet criteria for a Cannabis Use Disorder (CUD) and that QoL would be lower among those who met criteria for a CUD. We conducted a systematic review, employing guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The results were categorized into tables and identified trends. Fourteen studies met our pre-defined selection criteria. The studies were heterogeneous and their quality was low. With one exception, we did not identify any population for whom cannabis use was associated with improved QoL. QoL was lower in persons who used cannabis heavily, or who met criteria for CUD. However, this association was inconsistent and the magnitude was weaker than the relationship between QoL and use of other addictive substances (including tobacco and illicit drugs). In this systematic review, heavy cannabis use or CUD was associated with reduced QoL. It is unknown whether reduced QoL drives cannabis use, or whether cannabis use can lead to reduced QoL. Prospective studies are needed to evaluate the causal relationship between cannabis and QoL. Furthering the understanding of the relationship between cannabis and QoL can inform public policy, prevention efforts, outcomes, and an objective understanding of the effects of cannabis users. (Am J Addict 2017;26:8-25). © 2016 American Academy of Addiction Psychiatry.

Cannabis withdrawal in chronic, frequent cannabis smokers during sustained abstinence within a closed residential environment.

PubMed

Lee, Dayong; Schroeder, Jennifer R; Karschner, Erin L; Goodwin, Robert S; Hirvonen, Jussi; Gorelick, David A; Huestis, Marilyn A

2014-01-01

Chronic, frequent cannabis smokers may experience residual and offset effects, withdrawal, and craving when abstaining from the drug. We characterized the prevalence, duration, and intensity of these effects in chronic frequent cannabis smokers during abstinence on a closed research unit. Non-treatment-seeking participants (N = 29 on admission, 66% and 34% remaining after 2 and 4 weeks) provided subjective effects data. A battery of five instruments was computer-administered daily to measure psychological, sensory, and physical symptoms associated with cannabinoid intoxication and withdrawal. Plasma and oral fluid specimens were concurrently collected and analyzed for cannabinoids. Outcome variables were evaluated as change from admission (Day 0) with regression models. Most abstinence effects, including irritability and anxiety were greatest on Days 0-3 and decreased thereafter. Cannabis craving significantly decreased over time, whereas decreased appetite began to normalize on Day 4. Strange dreams and difficulty getting to sleep increased over time, suggesting intrinsic sleep problems in chronic cannabis smokers. Symptoms likely induced by residual drug effects were at maximum intensity on admission and positively correlated with plasma and oral fluid cannabinoid concentrations on admission but not afterward; these symptoms showed overall prevalence higher than cannabis withdrawal symptoms. The combined influence of residual/offset drug effects, withdrawal, and craving was observed in chronic cannabis smokers during monitored abstinence. Abstinence symptoms were generally more intense in the initial phase, implying importance of early intervention in cannabis quit attempts. Sleep disturbance persisting for an extended period suggests that hypnotic medications could be beneficial in treating cannabis dependence. © American Academy of Addiction Psychiatry.

Cannabis Withdrawal in Chronic, Frequent Cannabis Smokers during Sustained Abstinence within a Closed Residential Environment

PubMed Central

Lee, Dayong; Schroeder, Jennifer R.; Karschner, Erin L.; Goodwin, Robert S.; Hirvonen, Jussi; Gorelick, David A.; Huestis, Marilyn A.

2013-01-01

Objectives Chronic, frequent cannabis smokers may experience residual and offset effects, withdrawal, and craving when abstaining from the drug. We characterized the prevalence, duration, and intensity of these effects in chronic frequent cannabis smokers during abstinence on a closed research unit. Methods Non-treatment-seeking participants (N=29 on admission, 66% and 34% remaining after 2 and 4 weeks) provided subjective effects data. A battery of 5 instruments was computer-administered daily to measure psychological, sensory, and physical symptoms associated with cannabinoid intoxication and withdrawal. Plasma and oral fluid specimens were concurrently collected and analyzed for cannabinoids. Outcome variables were evaluated as change from admission (Day 0) with regression models. Results Most abstinence effects, including irritability and anxiety were greatest on Days 0–3 and decreased thereafter. Cannabis craving significantly decreased over time, whereas decreased appetite began to normalize on Day 4. Strange dreams and difficulty getting to sleep increased over time, suggesting intrinsic sleep problems in chronic cannabis smokers. Symptoms likely induced by residual drug effects were at maximum intensity on admission and positively correlated with plasma and oral fluid cannabinoid concentrations on admission but not afterward; these symptoms showed overall prevalence higher than cannabis withdrawal symptoms. Conclusions The combined influence of residual/offset drug effects, withdrawal and craving was observed in chronic cannabis smokers during monitored abstinence. Abstinence symptoms were generally more intense in the initial phase, implying importance of early intervention in cannabis quit attempts. Sleep disturbance persisting for an extended period suggests that hypnotic medications could be beneficial in treating cannabis dependence. PMID:24724880

Prevalence of Cannabis Use Disorder and Associated Factors among Cannabis Young Adult Users at Shashemene Town, Oromia Region, Ethiopia, 2016

PubMed Central

Tullu, Mikiyas; Azale, Telake; Solomon, Haddis; Habtamu, Yodit

2018-01-01

Introduction Cannabis users are at high risk of developing cannabis use disorder which is a problematic pattern of cannabis use leading to clinically significant impairment or distress. Objective To assess the magnitude of cannabis use disorder and associated factors among young adults using cannabis at Shashemene Town, Oromia Region, Ethiopia. Methods A cross-sectional study was conducted at Shashemene Town, from May to June 2016. Young adults aged 18–25 who use cannabis and are permanent residents of Shashemene were included in the study. Using single proportion formula, 423 participants were selected using exponential discriminative snow ball sampling. Result This study revealed that the magnitude of cannabis use disorder was 42.2%. The most contributing factors that remained to be statistically significant with cannabis use disorder were common mental disorder (AOR = 2.125, 95% CI: 1.218, 3.708), current cigarette smoking (AOR = 6.118, 95% CI: 2.13, 17.575), and current use of shisha (AOR = 4.313, 95% CI: 2.427, 7.664). Conclusion The magnitude of cannabis use disorder among young adults using cannabis was high. PMID:29670893

Prospective Assessment of Cannabis Withdrawal in Adolescents with Cannabis Dependence: A Pilot Study

ERIC Educational Resources Information Center

Milin, Robert; Manion, Ian; Dare, Glenda; Walker, Selena

2008-01-01

A study to identify and assess the withdrawal symptoms in adolescents afflicted with cannabis dependence is conducted. Results conclude that withdrawal symptoms of cannabis were present in adolescents seeking treatment for this substance abuse.

Position statement on cannabis.

PubMed

Stein, Dan Joseph

2016-05-16

There is an ongoing national debate around cannabis policy. This brief position statement by the Executive Committee of the Central Drug Authorityoutlines some of the factors that have contributed to this debate, delineates reduction strategies, summarises the harms and benefits ofmarijuana, and provides recommendations. These recommendations emphasise an integrated and evidence-based approach, the need forresources to implement harm reduction strategies against continued and chronic use of alcohol and cannabis, and the potential value of afocus on decriminalisation rather than the legalisation of cannabis.

Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa

PubMed Central

Imam, Aminu; Ajao, Moyosore Saliu; Amin, Abdulbasit; Abdulmajeed, Wahab Imam; Ibrahim, Abdulmumin; Olajide, Olayemi Joseph; Ajibola, Musa Iyiola; Alli-Oluwafuyi, Abdulmusawir; Balogun, Wasiu Gbolahan

2016-01-01

Background Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. Methods Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days. The Morris water maze (MWM) paradigm was used to assess the memory index, the elevated plus maze was used for anxiety-like behaviour, and the open field test was used for locomotor activities; thereafter, the rats were sacrificed and their brains were removed for histopathologic studies. Results Cannabis-like Scopolamine caused memory impairment, delayed latency in the MWM, and anxiety-like behaviour, coupled with alterations in the cerebello-hippocampal neurons. The post-treatment of rats with NSO mitigated cannabis-induced cognitive dysfunction as with scopolamine and impaired anxiety-like behaviour by increasing open arm entry, line crossing, and histological changes. Conclusions The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis. PMID:27904421

Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa.

PubMed

Imam, Aminu; Ajao, Moyosore Saliu; Amin, Abdulbasit; Abdulmajeed, Wahab Imam; Ibrahim, Abdulmumin; Olajide, Olayemi Joseph; Ajibola, Musa Iyiola; Alli-Oluwafuyi, Abdulmusawir; Balogun, Wasiu Gbolahan

2016-09-01

Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days. The Morris water maze (MWM) paradigm was used to assess the memory index, the elevated plus maze was used for anxiety-like behaviour, and the open field test was used for locomotor activities; thereafter, the rats were sacrificed and their brains were removed for histopathologic studies. Cannabis-like Scopolamine caused memory impairment, delayed latency in the MWM, and anxiety-like behaviour, coupled with alterations in the cerebello-hippocampal neurons. The post-treatment of rats with NSO mitigated cannabis-induced cognitive dysfunction as with scopolamine and impaired anxiety-like behaviour by increasing open arm entry, line crossing, and histological changes. The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis.

US Epidemiology of Cannabis Use and Associated Problems

PubMed Central

Hasin, Deborah S

2018-01-01

This review provides an overview of the changing US epidemiology of cannabis use and associated problems. Adults and adolescents increasingly view cannabis as harmless, and some can use cannabis without harm. However, potential problems include harms from prenatal exposure and unintentional childhood exposure; decline in educational or occupational functioning after early adolescent use, and in adulthood, impaired driving and vehicle crashes; cannabis use disorders (CUD), cannabis withdrawal, and psychiatric comorbidity. Evidence suggests national increases in cannabis potency, prenatal and unintentional childhood exposure; and in adults, increased use, CUD, cannabis-related emergency room visits, and fatal vehicle crashes. Twenty-nine states have medical marijuana laws (MMLs) and of these, 8 have recreational marijuana laws (RMLs). Many studies indicate that MMLs or their specific provisions did not increase adolescent cannabis use. However, the more limited literature suggests that MMLs have led to increased cannabis potency, unintentional childhood exposures, adult cannabis use, and adult CUD. Ecological-level studies suggest that MMLs have led to substitution of cannabis for opioids, and also possibly for psychiatric medications. Much remains to be determined about cannabis trends and the role of MMLs and RMLs in these trends. The public, health professionals, and policy makers would benefit from education about the risks of cannabis use, the increases in such risks, and the role of marijuana laws in these increases. PMID:28853439

Cannabis Withdrawal, Posttreatment Abstinence, and Days to First Cannabis Use Among Emerging Adults in Substance Use Treatment: A Prospective Study

PubMed Central

Davis, Jordan P.; Smith, Douglas C.; Morphew, Jason W.; Lei, Xinrong; Zhang, Saijun

2015-01-01

Very little prospective research investigates how cannabis withdrawal is associated with treatment outcomes, and this work has not used the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) thresholds for cannabis withdrawal. The sample included 110 emerging adults entering outpatient substance use treatment who were heavy cannabis users with no other drug use and limited alcohol use. We used survival analyses to predict days to first use of cannabis and logistic regression to predict whether participants were abstinent and living in the community at 3 months. Those meeting criteria for cannabis withdrawal were more likely to return to use sooner than those not meeting criteria for cannabis withdrawal. However, the presence of cannabis withdrawal was not a significant predictor of 3-month abstinence. Emerging adults with DSM-5 cannabis withdrawal may have difficulty initiating abstinence in the days following their intake assessment, implying the need for strategies to mitigate their more rapid return to cannabis use. PMID:26877548

Weeding Out the Truth: Adolescents and Cannabis.

PubMed

Ammerman, Seth; Tau, Gregory

2016-01-01

The use of cannabis for both legal (similar to alcohol) and medical purposes is becoming more common. Although cannabis remains an illegal Schedule 1 drug federally, as of November 2015, 23 states and the District of Columbia have legalized "medical" cannabis, and 4 states and the District of Columbia have legalized the use of cannabis for adults aged 21 years and older. It is very likely that more and more states will sooner rather than later allow cannabis for both medical and legal purposes. This review article will focus on a variety of issues relevant to the current debate about cannabis, and will address the following.

Presentations to the Emergency Department Following Cannabis use--a Multi-Centre Case Series from Ten European Countries.

PubMed

Dines, Alison M; Wood, David M; Galicia, Miguel; Yates, Christopher M; Heyerdahl, Fridtjof; Hovda, Knut Erik; Giraudon, Isabelle; Sedefov, Roumen; Dargan, Paul I

2015-12-01

Cannabis is the most commonly used illicit drug in Europe, and is generally regarded as having low acute toxicity. We present the findings of the first 6 months of data collection from the Euro-DEN project on presentations related to cannabis use to further understand the acute toxicity related to the use of cannabis. Data was extracted on clinical features, treatment and outcome from the Euro-DEN minimum dataset for all cases of acute recreational drug toxicity reported 1st October 2013 to 31st March 2014 for all cannabis-related presentations. Of 2198 presentations reported by 14 of the 16 Euro-DEN centres, 356 (16.2 %) involved cannabis either alone or together with other drugs/alcohol. There were 36 that involved lone use of cannabis (1.6 % of all presentations). Of the 35 non-fatal lone cannabis presentations, the most commonly reported features were neuro-behavioural (agitation/aggression 8 (22.9 %), psychosis 7 (20.0 %), anxiety 7 (20.0 %)) and vomiting 6 (17.1 %). Most patients (25, 71.4 %) received no treatment and 30 (85.7 %) were discharged/self-discharged from the ED. There was one fatality amongst these lone-cannabis cases: an 18-year-old male collapsed with an asystolic cardiac arrest whilst smoking cannabis and suffered hypoxic brain injury related to prolonged cardiac arrest. THC was detected in a urine sample taken at ED arrival; no other drugs were detected. Lone acute cannabis toxicity was typically associated with neuro-behavioural symptoms and vomiting. Although uncommon, severe toxicity including cardiovascular toxicity and death may be under-recognised, and it is important that Emergency Physicians are aware of this.

Efficacy of CBD-enriched medical cannabis for treatment of refractory epilepsy in children and adolescents - An observational, longitudinal study.

PubMed

Hausman-Kedem, Moran; Menascu, Shay; Kramer, Uri

2018-04-16

The objective of this observational study was to evaluate the efficacy of medical cannabis for the treatment of refractory epilepsy. Fifty-seven patients (age 1-20 years) with epilepsy of various etiologies were treated with Cannabis oil extract (CBD/THC ratio of 20:1) for at least 3 months (Median follow up time-18 months). Forty-Six Patients were included in the efficacy analysis. Average CBD dose was11.4 mg/kg/d. Twenty-six patients (56%) had ≤50% reduction in mean monthly seizure frequency. There was no statistically significant difference in response rate among various epilepsy etiologies, and cannabis strain used. Younger age at treatment onset (<10 years) and higher CBD dose (>11 mg/kg/d) were associated with better response to treatment. Adverse reactions were reported in 46% of patients and were the main reason for treatment cessation. Our results suggest that adding CBD-enriched cannabis extract to the treatment regimen of patients with refractory epilepsy may result in a significant reduction in seizure frequency according to parental reports. Randomized controlled trials are necessary to assess its true efficacy. Copyright © 2018 Elsevier B.V. All rights reserved.

Online survey characterizing vaporizer use among cannabis users.

PubMed

Lee, Dustin C; Crosier, Benjamin S; Borodovsky, Jacob T; Sargent, James D; Budney, Alan J

2016-02-01

Along with changes in cannabis laws in the United States and other countries, new products for consuming cannabis are emerging, with unclear public health implications. Vaporizing or "vaping" cannabis is gaining popularity, but little is known about its prevalence or consequences. This study characterized the prevalence and current patterns of vaping cannabis among a large national sample of cannabis users. An online survey was distributed through Facebook ads targeting individuals with interests related to cannabis use. The sample comprised 2910 cannabis users (age: 18-90, 84% male, 74% Caucasian). A majority (61%) endorsed lifetime prevalence of ever vaping, 37% reported vaping in the past 30 days, 20% reported vaping more than 100 lifetime days, and 12% endorsed vaping as their preferred method. Compared to those that had never vaped, vaporizer users were younger, more likely to be male, initiated cannabis at an earlier age, and were less likely to be African American. Those that preferred vaping reported it to be healthier, better tasting, produced better effects, and more satisfying. Only 14% reported a reduction in smoking cannabis since initiating vaping, and only 5% mixed cannabis with nicotine in a vaporizer. Many cannabis users report vaping cannabis, but currently only a small subset prefers vaping to smoking and reports frequent vaping. Increases in availability and marketing of vaping devices, and the changing legal status of cannabis in the United States and other countries may influence patterns of use. Frequent monitoring is needed to assess the impact of changing cannabis laws and regulations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Online Survey Characterizing Vaporizer Use among Cannabis Users

PubMed Central

Lee, Dustin C.; Crosier, Benjamin S.; Borodovsky, Jacob T.; Sargent, James D.; Budney, Alan J.

2016-01-01

Background Along with changes in cannabis laws in the United States and other countries, new products for consuming cannabis are emerging, with unclear public health implications. Vaporizing or “vaping” cannabis is gaining popularity, but little is known about its prevalence or consequences. Methods This study characterized the prevalence and current patterns of vaping cannabis among a large national sample of cannabis users. An online survey was distributed through Facebook ads targeting individuals with interests related to cannabis use. The sample comprised 2,910 cannabis users (age: 18-90, 84% male, 74% Caucasian). Results A majority (61%) endorsed lifetime prevalence of ever vaping, 37% reported vaping in the past 30 days, 20% reported vaping more than 100 lifetime days, and 12% endorsed vaping as their preferred method. Compared to those that had never vaped, vaporizer users were younger, more likely to be male, initiated cannabis at an earlier age, and were less likely to be African American. Those that preferred vaping reported it to be healthier, better tasting, produced better effects, and more satisfying. Only 14% reported a reduction in smoking cannabis since initiating vaping, and only 5% mixed cannabis with nicotine in a vaporizer. Many cannabis users report vaping cannabis, but currently only a small subset prefers vaping to smoking and reports frequent vaping. Conclusion Increases in availability and marketing of vaping devices, and the changing legal status of cannabis in the United States and other countries may influence patterns of use. Frequent monitoring is needed to assess the impact of changing cannabis laws and regulations. PMID:26774946

Synthetic cannabis and respiratory depression.

PubMed

Jinwala, Felecia N; Gupta, Mayank

2012-12-01

In recent years, synthetic cannabis use has been increasing in appeal among adolescents, and its use is now at a 30 year peak among high school seniors. The constituents of synthetic cannabis are difficult to monitor, given the drug's easy accessibility. Currently, 40 U.S. states have banned the distribution and use of some known synthetic cannabinoids, and have included these drugs in the Schedule I category. The depressive respiratory effect in humans caused by synthetic cannabis inhalation has not been thoroughly investigated in the medical literature. We are the first to report, to our knowledge, two cases of self-reported synthetic cannabis use leading to respiratory depression and necessary intubation.

Schizophrenia and cannabis use.

PubMed

Kumra, Sanjiv

2007-01-01

Genetic predisposition and environmental risk factors are thought to play a role in the pathophysiology of schizophrenia. Exposure to cannabis is one environmental factor that's being studied for its possible link to development of schizophrenia in adolescents. This article presents evidence that supports the hypothesis that repeated cannabis use could interfere with the development of frontal white matter in some adolescents and may exacerbate anatomic pathology in those with schizophrenia. This putative mechanism may explain the deficits in working memory and worsening in the severity of clinical symptoms in adolescents with schizophrenia who use cannabis.

Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life.

PubMed

Fiz, Jimena; Durán, Marta; Capellà, Dolors; Carbonell, Jordi; Farré, Magí

2011-04-21

The aim of this study was to describe the patterns of cannabis use and the associated benefits reported by patients with fibromyalgia (FM) who were consumers of this drug. In addition, the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users. Information on medicinal cannabis use was recorded on a specific questionnaire as well as perceived benefits of cannabis on a range of symptoms using standard 100-mm visual analogue scales (VAS). Cannabis users and non-users completed the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI) and the Short Form 36 Health Survey (SF-36). Twenty-eight FM patients who were cannabis users and 28 non-users were included in the study. Demographics and clinical variables were similar in both groups. Cannabis users referred different duration of drug consumption; the route of administration was smoking (54%), oral (46%) and combined (43%). The amount and frequency of cannabis use were also different among patients. After 2 hours of cannabis use, VAS scores showed a statistically significant (p<0.001) reduction of pain and stiffness, enhancement of relaxation, and an increase in somnolence and feeling of well being. The mental health component summary score of the SF-36 was significantly higher (p<0.05) in cannabis users than in non-users. No significant differences were found in the other SF-36 domains, in the FIQ and the PSQI. The use of cannabis was associated with beneficial effects on some FM symptoms. Further studies on the usefulness of cannabinoids in FM patients as well as cannabinoid system involvement in the pathophysiology of this condition are warranted.

The effects of prenatal cannabis exposure on fetal development and pregnancy outcomes: a protocol.

PubMed

Gunn, Jayleen K L; Rosales, Cecilia B; Center, Katherine E; Nuñez, Annabelle V; Gibson, Steven J; Ehiri, John E

2015-03-13

The effects of exposure to marijuana in utero on fetal development are not clear. Given that the recent legislation on cannabis in the US is likely to result in increased use, there is a need to assess the effects of prenatal cannabis exposure on fetal development and pregnancy outcomes. The objective of this review is to assess the effects of prenatal exposure to cannabis on pregnancy outcomes (including maternal and child outcomes). Major databases will be searched from inception to the latest issue, with the aim of identifying studies that reported the effects of prenatal exposure to cannabis on fetal development and pregnancy outcomes. Two investigators will independently review all titles and abstracts to identify potential articles. Discrepancies will be resolved by repeated review, discussion and consensus. Study quality assessment will be undertaken, using standard protocols. To qualify for inclusion, studies must report at least one maternal or neonatal outcome post partum. Cross-sectional, case-control, cohort and randomised controlled trials published in English will be included. In order to rule out the effects of other drugs that may affect fetal development and pregnancy outcomes, studies will only be included if they report outcomes of prenatal exposure to cannabis while excluding other illicit substances. Data from eligible studies will be extracted, and data analysis will include a systematic review and critical appraisal of evidence, and meta-analysis if data permit. Meta-analysis will be conducted if three or more studies report comparable statistics on the same outcome. The review which will result from this protocol has not already been conducted. Preparation of the review will follow the procedures stated in this protocol, and will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ethical approval of data will not be required since the review will use data that are already available in the

Oral fluid cannabinoids in chronic frequent cannabis smokers during ad libitum cannabis smoking

PubMed Central

Lee, Dayong; Vandrey, Ryan; Mendu, Damodara R.; Murray, Jeannie A.; Barnes, Allan J.; Huestis, Marilyn A.

2014-01-01

Background Oral fluid (OF) offers a simple, non-invasive and directly observable sample collection for clinical and forensic drug testing. Given that chronic cannabis smokers often engage in drug administration multiple times daily, evaluating OF cannabinoid pharmacokinetics during ad libitum smoking is important for practical development of analytical methods and informed interpretation of test results. Methods Eleven cannabis smokers resided on a closed research unit for 51 days, and underwent four 5-day oral delta-9-tetrahydrocannabinol (THC) treatments. Each medication period was separated by 9 days of ad libitum cannabis smoking from 12:00 to 23:00h daily. Ten OF samples were collected from 9:00–22:00h on each of the last ad libitum smoking days (Study Days 4, 18, 32, and 46). Results As the number of cannabis cigarettes smoked increased over study days, OF THC, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH) also increased with a significant effect of time since last smoking (∆time; range, 0.0–17.4h) and ≥88% detection rates; concentrations on Day 4 were significantly lower than those on Days 32 and 46 but not Day 18. Within 30 min post smoking, median THC, CBN, and THCCOOH concentrations were 689µg/L, 116µg/L, and 147ng/L, respectively, decreasing to 19.4µg/L, 2.4µg/L, and 87.6ng/L after 10h. Cannabidiol and 11-hydroxy-THC showed overall lower detection rates of 29 and 8.6%, respectively. Conclusions Cannabinoid disposition in OF was highly influenced by ∆time and composition of smoked cannabis. Furthermore, cannabinoid OF concentrations increased over ad libitum smoking days, in parallel with increased cannabis self-administration, possibly reflecting development of increased cannabis tolerance. PMID:25220020

Relation between cannabis use and subcortical volumes in people at clinical high risk of psychosis.

PubMed

Buchy, Lisa; Mathalon, Daniel H; Cannon, Tyrone D; Cadenhead, Kristin S; Cornblatt, Barbara A; McGlashan, Thomas H; Perkins, Diana O; Seidman, Larry J; Tsuang, Ming T; Walker, Elaine F; Woods, Scott W; Bearden, Carrie E; Addington, Jean

2016-08-30

Among people at genetic risk of schizophrenia, those who use cannabis show smaller thalamic and hippocampal volumes. We evaluated this relationship in people at clinical high risk (CHR) of psychosis. The Alcohol and Drug Use Scale was used to identify 132 CHR cannabis users, the majority of whom were non-dependent cannabis users, 387 CHR non-users, and 204 healthy control non-users, and all participants completed magnetic resonance imaging scans. Volumes of the thalamus, hippocampus and amygdala were extracted with FreeSurfer, and compared across groups. Comparing all CHR participants with healthy control participants revealed no significant differences in volumes of any ROI. However, when comparing CHR users to CHR non-users, a significant ROI×Cannabis group effect emerged: CHR users showed significantly smaller amygdala compared to CHR non-users. However, when limiting analysis to CHR subjects who reported using alcohol at a 'use without impairment' severity level, the amygdala effect was non-significant; rather, smaller hippocampal volumes were seen in CHR cannabis users compared to non-users. Controlling statistically for effects of alcohol and tobacco use rendered all results non-significant. These results highlight the importance of controlling for residual confounding effects of other substance use when examining the relationship between cannabis use and neural structure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Free and Glucuronide Whole Blood Cannabinoids' Pharmacokinetics after Controlled Smoked, Vaporized, and Oral Cannabis Administration in Frequent and Occasional Cannabis Users: Identification of Recent Cannabis Intake.

PubMed

Newmeyer, Matthew N; Swortwood, Madeleine J; Barnes, Allan J; Abulseoud, Osama A; Scheidweiler, Karl B; Huestis, Marilyn A

2016-12-01

There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Δ 9 -tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoids cannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for ≤2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Δ 9 -tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used. We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoids in occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration. Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC ≥5 μg/L plus THCCOOH/11-hydroxy-THC ratio <20 cutoff produced detection windows <8 h after all routes for frequent smokers; no occasional smoker was positive 1.5 h or 12 h following inhaled or oral cannabis, respectively. Vaporization and smoking provide comparable cannabinoid delivery. CBG and CBN are recent-use cannabis markers after cannabis inhalation, but their absence does not exclude recent use. Multiple, complimentary criteria should be implemented in conjunction with impairment observations to improve interpretation of cannabinoid tests. Clinicaltrials.gov Identifier: NCT02177513. © 2016 American Association for Clinical Chemistry.

Residual cannabis levels in blood, urine and oral fluid following heavy cannabis use.

PubMed

Odell, Morris S; Frei, Matthew Y; Gerostamoulos, Dimitri; Chu, Mark; Lubman, Dan I

2015-04-01

An understanding of tetrahydrocannabinol (THC) kinetics and residual levels after cannabis use is essential in interpreting toxicology tests in body fluids from live subjects, particularly when used in forensic settings for drug abuse, traffic and interpersonal violence cases. However the current literature is largely based on laboratory studies using controlled cannabis dosages in experienced users, with limited research investigating the kinetics of residual THC concentrations in regular high dose cannabis users. Twenty-one dependent cannabis users were recruited at admission to two residential detoxification units in Melbourne, Australia. After being provided with information about, and consenting to, the study, subjects volunteered to provide once-daily blood, urine and oral fluid (saliva) samples for seven consecutive days following admission, involving cessation and abstinence from all cannabis use. Blood and oral fluid specimens were analysed for THC and urine specimens for the metabolite THC-COOH. In some subjects THC was detectable in blood for at least 7 days and oral fluid specimens were positive for THC up to 78 h after admission to the unit. Urinary THC-COOH concentrations exceeded 1000 ng/mL for some subjects 129 h after last use. The presented blood THC levels are higher and persist longer in some individuals than previously described, our understanding and interpretation of THC levels in long term heavy cannabis users may need to be reconsidered. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Phytochemistry of Cannabis sativa L.

PubMed

ElSohly, Mahmoud A; Radwan, Mohamed M; Gul, Waseem; Chandra, Suman; Galal, Ahmed

Cannabis (Cannabis sativa, or hemp) and its constituents-in particular the cannabinoids-have been the focus of extensive chemical and biological research for almost half a century since the discovery of the chemical structure of its major active constituent, Δ 9 -tetrahydrocannabinol (Δ 9 -THC). The plant's behavioral and psychotropic effects are attributed to its content of this class of compounds, the cannabinoids, primarily Δ 9 -THC, which is produced mainly in the leaves and flower buds of the plant. Besides Δ 9 -THC, there are also non-psychoactive cannabinoids with several medicinal functions, such as cannabidiol (CBD), cannabichromene (CBC), and cannabigerol (CBG), along with other non-cannabinoid constituents belonging to diverse classes of natural products. Today, more than 560 constituents have been identified in cannabis. The recent discoveries of the medicinal properties of cannabis and the cannabinoids in addition to their potential applications in the treatment of a number of serious illnesses, such as glaucoma, depression, neuralgia, multiple sclerosis, Alzheimer's, and alleviation of symptoms of HIV/AIDS and cancer, have given momentum to the quest for further understanding the chemistry, biology, and medicinal properties of this plant.This contribution presents an overview of the botany, cultivation aspects, and the phytochemistry of cannabis and its chemical constituents. Particular emphasis is placed on the newly-identified/isolated compounds. In addition, techniques for isolation of cannabis constituents and analytical methods used for qualitative and quantitative analysis of cannabis and its products are also reviewed.

Reactivity to Cannabis Cues in Virtual Reality Environments†

PubMed Central

Bordnick, Patrick S.; Copp, Hilary L.; Traylor, Amy; Graap, Ken M.; Carter, Brian L.; Walton, Alicia; Ferrer, Mirtha

2014-01-01

Virtual reality (VR) cue environments have been developed and successfully tested in nicotine, cocaine, and alcohol abusers. Aims in the current article include the development and testing of a novel VR cannabis cue reactivity assessment system. It was hypothesized that subjective craving levels and attention to cannabis cues would be higher in VR environments merits with cannabis cues compared to VR neutral environments. Twenty nontreatment-seeking current cannabis smokers participated in the VR cue trial. During the VR cue trial, participants were exposed to four virtual environments that contained audio, visual, olfactory, and vibrotactile sensory stimuli. Two VR environments contained cannabis cues that consisted of a party room in which people were smoking cannabis and a room containing cannabis paraphernalia without people. Two VR neutral rooms without cannabis cues consisted of a digital art gallery with nature videos. Subjective craving and attention to cues were significantly higher in the VR cannabis environments compared to the VR neutral environments. These findings indicate that VR cannabis cue reactivity may offer a new technology-based method to advance addiction research and treatment. PMID:19705672

Cognitive measures in long-term cannabis users.

PubMed

Pope, Harrison G; Gruber, Amanda J; Hudson, James I; Huestis, Marilyn A; Yurgelun-Todd, Deborah

2002-11-01

The cognitive effects of long-term cannabis use are insufficiently understood. Most studies concur that cognitive deficits persist at least several days after stopping heavy cannabis use. But studies differ on whether such deficits persist long term or whether they are correlated with increasing duration of lifetime cannabis use. The authors administered neuropsychological tests to 77 current heavy cannabis users who had smoked cannabis at least 5000 times in their lives, and to 87 control subjects who had smoked no more than 50 times in their lives. The heavy smokers showed deficits on memory of word lists on Days 0, 1, and 7 of a supervised abstinence period. By Day 28, however, few significant differences were found between users and controls on the test measures, and there were few significant associations between total lifetime cannabis consumption and test performance. Although these findings may be affected by residual confounding, as in all retrospective studies, they suggest that cannabis-associated cognitive deficits are reversible and related to recent cannabis exposure rather than irreversible and related to cumulative lifetime use.

Cannabis craving in response to laboratory-induced social stress among racially diverse cannabis users: The impact of social anxiety disorder

PubMed Central

Buckner, Julia D; Zvolensky, Michael J; Ecker, Anthony H; Jeffries, Emily R

2016-01-01

Social anxiety disorder appears to be a risk factor for cannabis-related problems. Although it is presumed that increases in cannabis craving during elevated social anxiety reflect an intent to cope with greater negative affectivity, it is unclear whether increases in physiological arousal during social stress are related to cannabis craving, especially among those with social anxiety disorder. Similarly, no studies have assessed motivational reasons for cannabis use during elevated social stress. Thus, the current study tested whether increases in state social anxiety (measured subjectively and via physiological arousal) were related to greater cannabis craving among 126 current cannabis users (88.9% with cannabis use disorder, 31.7% with social anxiety disorder, 54.0% non-Hispanic Caucasian) randomly assigned to either a social interaction or reading task. As predicted, cannabis users in the social interaction condition reported greater cannabis craving than those in the reading condition. This effect was particularly evident among those with social anxiety disorder. Although physiological arousal did not moderate the relationship between condition and craving, coping motives were the most common reasons cited for wanting to use cannabis and were reported more among those in the social interaction task. These experimental results uniquely add to a growing literature suggesting the importance of elevated state social anxiety (especially among those with social anxiety disorder) in cannabis use vulnerability processes. PMID:26839322

Cannabis craving in response to laboratory-induced social stress among racially diverse cannabis users: The impact of social anxiety disorder.

PubMed

Buckner, Julia D; Zvolensky, Michael J; Ecker, Anthony H; Jeffries, Emily R

2016-04-01

Social anxiety disorder appears to be a risk factor for cannabis-related problems. Although it is presumed that increases in cannabis craving during elevated social anxiety reflect an intent to cope with greater negative affectivity, it is unclear whether increases in physiological arousal during social stress are related to cannabis craving, especially among those with social anxiety disorder. Similarly, no studies have assessed motivational reasons for cannabis use during elevated social stress. Thus, the current study tested whether increases in state social anxiety (measured subjectively and via physiological arousal) were related to greater cannabis craving among 126 current cannabis users (88.9% with cannabis use disorder, 31.7% with social anxiety disorder, 54.0% non-Hispanic Caucasian) randomly assigned to either a social interaction or reading task. As predicted, cannabis users in the social interaction condition reported greater cannabis craving than those in the reading condition. This effect was particularly evident among those with social anxiety disorder. Although physiological arousal did not moderate the relationship between condition and craving, coping motives were the most common reasons cited for wanting to use cannabis and were reported more among those in the social interaction task. These experimental results uniquely add to a growing literature suggesting the importance of elevated state social anxiety (especially among those with social anxiety disorder) in cannabis use vulnerability processes. © The Author(s) 2016.

[Cannabis use and impairment of respiratory function].

PubMed

Underner, M; Urban, T; Perriot, J; Peiffer, G; Meurice, J-C

2013-04-01

Cannabis is the most commonly smoked illicit substance in many countries including France. It can be smoked alone in plant form (marijuana) but in our country it is mainly smoked in the form of cannabis resin mixed with tobacco. The technique of inhaling cannabis differs from that of tobacco, increasing the time that the smoke spends in contact with the bronchial mucosal and its impact on respiratory function. One cigarette composed of cannabis and tobacco is much more harmful than a cigarette containing only tobacco. In cannabis smokers there is an increased incidence of respiratory symptoms and episodes of acute bronchitis. Cannabis produces a rapid bronchodilator effect; chronic use provokes a reduction in specific conductance and increase in airways resistance. Studies on the decline of Forced Expiratory Volume are discordant. Cannabis smoke and tetrahydrocannabinol irritate the bronchial tree. They bring about histological signs of airways inflammation and alter the fungicidal and antibacterial activity of alveolar macrophages. Inhalation of cannabis smoke is a risk factor for lung cancer. Stopping smoking cannabis will bring about important benefits for lung function. This should encourage clinicians to offer patients support in quitting smoking. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues

PubMed Central

Russo, Ethan B.

2016-01-01

This overview covers a wide range of cannabis topics, initially examining issues in dispensaries and self-administration, plus regulatory requirements for production of cannabis-based medicines, particularly the Food and Drug Administration “Botanical Guidance.” The remainder pertains to various cannabis controversies that certainly require closer examination if the scientific, consumer, and governmental stakeholders are ever to reach consensus on safety issues, specifically: whether botanical cannabis displays herbal synergy of its components, pharmacokinetics of cannabis and dose titration, whether cannabis medicines produce cyclo-oxygenase inhibition, cannabis-drug interactions, and cytochrome P450 issues, whether cannabis randomized clinical trials are properly blinded, combatting the placebo effect in those trials via new approaches, the drug abuse liability (DAL) of cannabis-based medicines and their regulatory scheduling, their effects on cognitive function and psychiatric sequelae, immunological effects, cannabis and driving safety, youth usage, issues related to cannabis smoking and vaporization, cannabis concentrates and vape-pens, and laboratory analysis for contamination with bacteria and heavy metals. Finally, the issue of pesticide usage on cannabis crops is addressed. New and disturbing data on pesticide residues in legal cannabis products in Washington State are presented with the observation of an 84.6% contamination rate including potentially neurotoxic and carcinogenic agents. With ongoing developments in legalization of cannabis in medical and recreational settings, numerous scientific, safety, and public health issues remain. PMID:27683558

Pathways to psychosis in cannabis abuse.

PubMed

Shrivastava, Amresh; Johnston, Megan; Terpstra, Kristen; Bureau, Yves

2015-04-01

Cannabis has been implicated as a risk factor for the development of schizophrenia, but the exact biological mechanisms remain unclear. In this review, we attempt to understand the neurobiological pathways that link cannabis use to schizophrenia. This has been an area of great debate; despite similarities between cannabis users and schizophrenia patients, the evidence is not sufficient to establish cause-and-effect. There have been advances in the understanding of the mechanisms of cannabis dependence as well as the role of the cannabinoid system in the development of psychosis and schizophrenia. The neurobiological mechanisms associated with the development of psychosis and effects from cannabis use may be similar but remain elusive. In order to better understand these associations, this paper will show common neurobiological and neuroanatomical changes as well as common cognitive dysfunction in cannabis users and patients of schizophrenia. We conclude that epidemiologic evidence highlights potential causal links; however, neurobiological evidence for causality remains weak.

The New Cannabis Policy Taxonomy on APIS: Making Sense of the Cannabis Policy Universe.

PubMed

Klitzner, Michael D; Thomas, Sue; Schuler, Jonathan; Hilton, Michael; Mosher, James

2017-06-01

The National Institute on Alcohol Abuse and Alcoholism's Alcohol Policy Information System (APIS) is, for the first time, adding legal data pertaining to recreational cannabis use to its current offerings on alcohol policy. Now that Colorado, Washington, Oregon, Alaska, and the District of Columbia have legalized aspects of recreational cannabis, and more states are considering it, there is an urgency to provide high-quality, multi-dimensional legal data to the public health community. This article introduces the Cannabis Policy Taxonomy recently posted on APIS, and explores its theoretical and empirical contributions to the substance abuse literature and its potential for use in policy research. We also present results of interviews with public health experts in alcohol and cannabis policy, which sought to determine the most important variables to address in the initial release of cannabis policy data. From this process, we found that pricing controls emerged as the variable singled out by the largest number of experts. This analysis points to a host of vital policies that are of increasing importance to public health policy scholars and their current and future research.

Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients.

PubMed

Lucas, Philippe; Walsh, Zach

2017-04-01

In 2014 Health Canada replaced the Marihuana for Medical Access Regulations (MMAR) with the Marihuana for Medical Purposes Regulations (MMPR). One of the primary changes in the new program has been to move from a single Licensed Producer (LP) of cannabis to multiple Licensed Producers. This is the first comprehensive survey of patients enrolled in the MMPR. Patients registered to purchase cannabis from Tilray, a federally authorized Licenced Producer (LP) within the MMPR, were invited to complete an online survey consisting of 107 questions on demographics, patterns of use, and cannabis substitution effect. The survey was completed by 271 respondents. Cannabis is perceived to be an effective treatment for diverse conditions, with pain and mental health the most prominent. Findings include high self-reported use of cannabis as a substitute for prescription drugs (63%), particularly pharmaceutical opioids (30%), benzodiazepines (16%), and antidepressants (12%). Patients also reported substituting cannabis for alcohol (25%), cigarettes/tobacco (12%), and illicit drugs (3%). A significant percentage of patients (42%) reported accessing cannabis from illegal/unregulated sources in addition to access via LPs, and over half (55%) were charged to receive a medical recommendation to use cannabis, with nearly 25% paying $300 or more. The finding that patients report its use as a substitute for prescription drugs supports prior research on medical cannabis users; however, this study is the first to specify the classes of prescription drugs for which cannabis it is used as a substitute, and to match this substitution to specific diagnostic categories. The findings that some authorized patients purchase cannabis from unregulated sources and that a significant percentage of patients were charged for medical cannabis recommendations highlight ongoing policy challenges for this federal program. Copyright © 2017 Elsevier B.V. All rights reserved.

Attitudes to legalizing cannabis use.

PubMed

Williams, Jenny; van Ours, Jan C; Grossman, Michael

2016-09-01

In this paper, we investigate the relationship between cannabis use and attitudes to legalizing the use of cannabis. Predictions from theory provide a means of learning about the roles of information, self interest and regret in explaining differences in attitudes to legalization between those who currently use, those who have used in the past and those who have never used. Our empirical investigation suggests that users have a greater awareness of cannabis not being as harmful as abstainers think it is. This may explain why individuals are more inclined to be in favor of legalizing cannabis once they have used it themselves. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Expected impacts of the Cannabis Infringement Notice scheme in Western Australia on regular users and their involvement in the cannabis market.

PubMed

Chanteloup, Francoise; Lenton, Simon; Fetherston, James; Barratt, Monica J

2005-07-01

The effect on the cannabis market is one area of interest in the evaluation of the new 'prohibition with civil penalties' scheme for minor cannabis offences in WA. One goal of the scheme is to reduce the proportion of cannabis consumed that is supplied by large-scale suppliers that may also supply other drugs. As part of the pre-change phase of the evaluation, 100 regular (at least weekly) cannabis users were given a qualitative and quantitative interview covering knowledge and attitudes towards cannabis law, personal cannabis use, market factors, experience with the justice system and impact of legislative change. Some 85% of those who commented identified the changes as having little impact on their cannabis use. Some 89% of the 70 who intended to cultivate cannabis once the CIN scheme was introduced suggested they would grow cannabis within the two non-hydroponic plant-limit eligible for an infringement notice under the new law. Only 15% believed an increase in self-supply would undermine the large scale suppliers of cannabis in the market and allow some cannabis users to distance themselves from its unsavoury aspects. Only 11% said they would enter, or re-enter, the cannabis market as sellers as a result of the scheme introduction. Most respondents who commented believed that the impact of the legislative changes on the cannabis market would be negligible. The extent to which this happens will be addressed in the post-change phase of this research. Part of the challenge in assessing the impact of the CIN scheme on the cannabis market is that it is distinctly heterogeneous.

Cannabis Smoking and Cardiovascular Health: It's Complicated.

PubMed

Piano, M R

2017-08-01

Many states have legalized cannabis use for treatment of certain medical conditions or have legalized cannabis for recreational use. Consequently, cannabis use prevalence has escalated, giving rise to concerns about potential health effects. Cannabis smoking remains the most prevalent route of administration and is associated with inhalation of chemical toxicants. The aim of this article is to summarize the effects of cannabis smoking on the vasculature and occurrence of cardiovascular (CV) events such as myocardial infarction (MI) and stroke. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Measuring cannabis consumption: Psychometric properties of the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU).

PubMed

Cuttler, Carrie; Spradlin, Alexander

2017-01-01

We created the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU) because the current lack of psychometrically sound inventories for measuring these dimensions of cannabis use has impeded research on the effects of cannabis in humans. A sample of 2,062 cannabis users completed the DFAQ-CU and was used to assess the DFAQ-CU's factor structure and reliability. To assess validity, a subsample of 645 participants completed additional measures of cannabis dependence and problems (Marijuana Smoking History Questionnaire [MSHQ], Timeline Followback [TLFB], Cannabis Abuse Screening Test [CAST], Cannabis Use Disorders Identification Test Revised [CUDIT-R], Cannabis Use Problems Identification Test [CUPIT], and Alcohol Use Disorder Identification Test [AUDIT]). A six-factor structure was revealed, with factors measuring: daily sessions, frequency, age of onset, marijuana quantity, cannabis concentrate quantity, and edibles quantity. The factors were reliable, with Cronbach's alpha coefficients ranging from .69 (daily sessions) to .95 (frequency). Results further provided evidence for the factors' convergent (MSHQ, TLFB), predictive (CAST, CUDIT-R, CUPIT), and discriminant validity (AUDIT). The DFAQ-CU is the first psychometrically sound inventory for measuring frequency, age of onset, and quantity of cannabis use. It contains pictures of marijuana to facilitate the measurement of quantity of marijuana used, as well as questions to assess the use of different forms of cannabis (e.g., concentrates, edibles), methods of administering cannabis (e.g., joints, hand pipes, vaporizers), and typical THC levels. As such, the DFAQ-CU should help facilitate research on frequency, quantity, and age of onset of cannabis use.

Role of cannabis in cardiovascular disorders

PubMed Central

Awad, Hamza H.; Ghali, Jalal K.

2017-01-01

The growing popularity of medical and recreational consumption of cannabis, especially among the youth, raises immediate concerns regarding its safety and long-terms effects. The cardiovascular effects of cannabis are not well known. Cannabis consumption has been shown to cause arrhythmia including ventricular tachycardia, and potentially sudden death, and to increase the risk of myocardial infarction (MI). These effects appear to be compounded by cigarette smoking and precipitated by excessive physical activity, especially during the first few hours of consumption. Cannabinoids, or the active compounds of cannabis, have been shown to have heterogeneous effects on central and peripheral circulation. Acute cannabis consumption has been shown to cause an increase in blood pressure, specifically systolic blood pressure (SBP), and orthostatic hypotension. Cannabis use has been reported to increase risk of ischemic stroke, particularly in the healthy young patients. The endocannabinoid system (ECS) is currently considered as a promising therapeutic target in the management of several disease conditions. Synthetic cannabinoids (SCs) are being increasingly investigated for their therapeutic effects; however, the value of their benefits over possible complications remains controversial. Despite the considerable research in this field, the benefits of cannabis and its synthetic derivatives remains questionable even in the face of an increasingly tolerating attitude towards recreational consumption and promotion of the therapeutic complications. More efforts are needed to increase awareness among the public, especially youth, about the cardiovascular risks associated with cannabis use and to disseminate the accumulated knowledge regarding its ill effects. PMID:28840009

Role of cannabis in cardiovascular disorders.

PubMed

Goyal, Hemant; Awad, Hamza H; Ghali, Jalal K

2017-07-01

The growing popularity of medical and recreational consumption of cannabis, especially among the youth, raises immediate concerns regarding its safety and long-terms effects. The cardiovascular effects of cannabis are not well known. Cannabis consumption has been shown to cause arrhythmia including ventricular tachycardia, and potentially sudden death, and to increase the risk of myocardial infarction (MI). These effects appear to be compounded by cigarette smoking and precipitated by excessive physical activity, especially during the first few hours of consumption. Cannabinoids, or the active compounds of cannabis, have been shown to have heterogeneous effects on central and peripheral circulation. Acute cannabis consumption has been shown to cause an increase in blood pressure, specifically systolic blood pressure (SBP), and orthostatic hypotension. Cannabis use has been reported to increase risk of ischemic stroke, particularly in the healthy young patients. The endocannabinoid system (ECS) is currently considered as a promising therapeutic target in the management of several disease conditions. Synthetic cannabinoids (SCs) are being increasingly investigated for their therapeutic effects; however, the value of their benefits over possible complications remains controversial. Despite the considerable research in this field, the benefits of cannabis and its synthetic derivatives remains questionable even in the face of an increasingly tolerating attitude towards recreational consumption and promotion of the therapeutic complications. More efforts are needed to increase awareness among the public, especially youth, about the cardiovascular risks associated with cannabis use and to disseminate the accumulated knowledge regarding its ill effects.

Genetic identification of female Cannabis sativa plants at early developmental stage.

PubMed

Techen, Natascha; Chandra, Suman; Lata, Hemant; Elsohly, Mahmoud A; Khan, Ikhlas A

2010-11-01

Sequence-characterized amplified region (SCAR) markers were used to identify female plants at an early developmental stage in four different varieties of Cannabis sativa. Using the cetyl trimethylammonium bromide (CTAB) method, DNA was isolated from two-week-old plants of three drug-type varieties (Terbag W1, Terbag K2, and Terbag MX) and one fiber-type variety (Terbag Fedora A7) of C. sativa grown under controlled environmental conditions through seeds. Attempts to use MADC2 (male-associated DNA from Cannabis sativa) primers as a marker to identify the sex of Cannabis sativa plants were successful. Amplification of genomic DNA using MADC2-F and MADC2-R primers produced two distinct fragments, one with a size of approximately 450 bp for female plants and one for male plants with a size of approximately 300 bp. After harvesting the tissues for DNA extraction, plants were subjected to a flowering photoperiod (i.e., 12-h light cycle), and the appearance of flowers was compared with the DNA analysis. The results of the molecular analysis were found to be concordant with the appearance of male or female flowers. The results of this study represent a quick and reliable technique for the identification of sex in Cannabis plants using SCAR markers at a very early developmental stage. © Georg Thieme Verlag KG Stuttgart · New York.

Dose-dependent effects of cannabis on the neural correlates of error monitoring in frequent cannabis users.

PubMed

Kowal, Mikael A; van Steenbergen, Henk; Colzato, Lorenza S; Hazekamp, Arno; van der Wee, Nic J A; Manai, Meriem; Durieux, Jeffrey; Hommel, Bernhard

2015-11-01

Cannabis has been suggested to impair the capacity to recognize discrepancies between expected and executed actions. However, there is a lack of conclusive evidence regarding the acute impact of cannabis on the neural correlates of error monitoring. In order to contribute to the available knowledge, we used a randomized, double-blind, between-groups design to investigate the impact of administration of a low (5.5 mg THC) or high (22 mg THC) dose of vaporized cannabis vs. placebo on the amplitudes of the error-related negativity (ERN) and error positivity (Pe) in the context of the Flanker task, in a group of frequent cannabis users (required to use cannabis minimally 4 times a week, for at least 2 years). Subjects in the high dose group (n=18) demonstrated a significantly diminished ERN in comparison to the placebo condition (n=19), whereas a reduced Pe amplitude was observed in both the high and low dose (n=18) conditions, as compared to placebo. The results suggest that a high dose of cannabis may affect the neural correlates of both the conscious (late), as well as the initial automatic processes involved in error monitoring, while a low dose of cannabis might impact only the conscious (late) processing of errors. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Medicinal cannabis: rational guidelines for dosing.

PubMed

Carter, Gregory T; Weydt, Patrick; Kyashna-Tocha, Muraco; Abrams, Donald I

2004-05-01

The medicinal value of cannabis (marijuana) is well documented in the medical literature. Cannabinoids, the active ingredients in cannabis, have many distinct pharmacological properties. These include analgesic, anti-emetic, anti-oxidative, neuroprotective and anti-inflammatory activity, as well as modulation of glial cells and tumor growth regulation. Concurrent with all these advances in the understanding of the physiological and pharmacological mechanisms of cannabis, there is a strong need for developing rational guidelines for dosing. This paper will review the known chemistry and pharmacology of cannabis and, on that basis, discuss rational guidelines for dosing.

A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

PubMed Central

Wilsey, Barth; Marcotte, Thomas; Tsodikov, Alexander; Millman, Jeanna; Bentley, Heather; Gouaux, Ben; Fishman, Scott

2016-01-01

The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use “medical marijuana,” and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. PMID:18403272

Treatment of cannabis use among people with psychotic or depressive disorders: a systematic review.

PubMed

Baker, Amanda L; Hides, Leanne; Lubman, Dan I

2010-03-01

This article systematically reviews the evidence from randomized controlled trials (RCTs) for pharmacologic and psychological approaches to the treatment of cannabis use among individuals with psychotic or depressive disorders. A systematic literature search was conducted using the PubMed and PsychINFO databases from inception to December 2008. Individual searches in cannabis use (search terms: marijuana, cannabis, marijuana abuse, cannabis abuse, marijuana usage, cannabis usage), mental disorders (search terms: mood disorders, affective disorders, anxiety disorders, anxiety, depressive disorder, depression, psychotic disorders, psychosis, mental disorders), and pharmacotherapy (search terms: medication, drug therapy, pharmacotherapy, psychopharmacology, clinical trials, drug trial, treatment trial) were conducted and limited to humans, adolescents and adults. A search combining the individual cannabis use, mental disorder and pharmacotherapy searches produced 1,713 articles (PubMed = 1,398; PsychINFO = 315). Combining the cannabis use and mental disorder searches while limiting them to English articles and RCTs produced a total of 286 articles (PubMed = 228; PsychINFO = 58). From this literature, there were 7 RCTs conducted among mental health clients that reported cannabis use outcomes using pharmacologic or psychological interventions. While few RCTs have been conducted, there is evidence that pharmacologic and psychological interventions are effective for reducing cannabis use in the short-term among people with psychotic disorders or depression. Although it is difficult to make evidence-based treatment recommendations due to the paucity of research in this area, available studies indicate that effectively treating the mental health disorder with standard pharmacotherapy may be associated with a reduction in cannabis use and that longer or more intensive psychological interventions rather than brief interventions may be required, particularly among heavier

Cannabis and psychosis revisited.

PubMed

Damjanović, Aleksandar; Pantović, Maja; Damjanović, Aleksandra; Dunjić-Kostić, Bojana; Ivković, Maja; Milovanović, Srđan; Lacković, Maja; Dimitrijević, Ivan

2015-03-01

The association between cannabinoids and psychosis has been known for almost a thousand years, but it is still speculated whether cannabis use may be a contributory cause of psychosis, that is, whether it may precipitate schizophrenia in those at risk. In this paper, we will briefly present the data from individual longitudinal studies in the field, together with the factors that are considered important for the association of cannabis abuse and occurrence of schizophrenia and prevention opportunities in the target population. The reviewed studies clearly suggest that cannabis abuse predicts an increased risk for schizophrenia, particularly in young adults. They underline both the need to create adequate prevention measures and consequently avoid the occurrence of the disease in the young at risk. Particular attention should be additionally devoted toward encouraging the young presenting with psychotic symptoms to stop or, at the very least, reduce the frequency of cannabis abuse. The issues are undoubtedly to be addressed by the health care system in general.

Cannabis effects on driving lateral control with and without alcohol.

PubMed

Hartman, Rebecca L; Brown, Timothy L; Milavetz, Gary; Spurgin, Andrew; Pierce, Russell S; Gorelick, David A; Gaffney, Gary; Huestis, Marilyn A

2015-09-01

Effects of cannabis, the most commonly encountered non-alcohol drug in driving under the influence cases, are heavily debated. We aim to determine how blood Δ(9)-tetrahydrocannabinol (THC) concentrations relate to driving impairment, with and without alcohol. Current occasional (≥1×/last 3 months, ≤3days/week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500mg placebo, low (2.9%)-THC, or high (6.7%)-THC vaporized cannabis over 10min ad libitum in separate sessions (within-subject design, 6 conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives (∼0.8h duration). Blood, oral fluid (OF), and breath alcohol samples were collected before (0.17h, 0.42h) and after (1.4h, 2.3h) driving that occurred 0.5-1.3h after inhalation. We evaluated standard deviations of lateral position (lane weave, SDLP) and steering angle, lane departures/min, and maximum lateral acceleration. In N=18 completers (13 men, ages 21-37years), cannabis and alcohol increased SDLP. Blood THC concentrations of 8.2 and 13.1μg/L during driving increased SDLP similar to 0.05 and 0.08g/210L breath alcohol concentrations, the most common legal alcohol limits. Cannabis-alcohol SDLP effects were additive rather than synergistic, with 5μg/L THC+0.05g/210L alcohol showing similar SDLP to 0.08g/210L alcohol alone. Only alcohol increased lateral acceleration and the less-sensitive lane departures/min parameters. OF effectively documented cannabis exposure, although with greater THC concentration variability than paired blood samples. SDLP was a sensitive cannabis-related lateral control impairment measure. During drive blood THC ≥8.2μg/L increased SDLP similar to notably-impairing alcohol concentrations. Despite OF's screening value, OF variability poses challenges in concentration-based effects interpretation. Published by Elsevier Ireland Ltd.

Cannabis Use and Performance in Adolescents

ERIC Educational Resources Information Center

Malhotra, Anil; Biswas, Parthasarathy

2006-01-01

Cannabis is a widely used illicit drug among adolescents, many of whom perceive little risk from cannabis. Cannabis use is associated with poor academic performance and increased school drop-outs. It is also associated with high-risk behaviors in adolescents like crime, violence, unprotected sexual encounters, and car accidents. Many of these…

Does smoking cannabis affect work commitment?

PubMed

Hyggen, Christer

2012-07-01

  This study aimed to examine the associations between cannabis use and work commitment.   We used a 25-year panel survey initiated in 1985 with follow-ups in 1987, 1989, 1993, 2003 and 2010. Registered data from a range of public registers were matched with individual responses for the entire period.   The panel survey was a nation-wide study set in Norway.   A total of 1997 respondents born between 1965 and 1968 were included in the panel.   Work involvement scale (WIS) was used to assess work commitment. Involvement with cannabis was based on self-reported smoking of cannabis within the last 12 months and exposure to cannabis through friends. This information was categorized into 'abstaining', 'exposed', 'experimented' and 'involved'. Control measures included socio-economic background, mental health (HSCL-10), education, work satisfaction, unemployment, receipt of social assistance, consumption of alcohol, alcohol-related problems and use of other illicit drugs.   The level of work commitment was associated with involvement with cannabis. In 1993, when the respondents were in their mid-20s, those who were involved or had experimented with cannabis displayed lower levels of work commitment than those who were abstaining or merely exposed to cannabis through friends (P < 0.05). Work commitment among those who experimented with cannabis converged towards the levels reported by abstainers and the exposed as they grew older, whereas those involved reported decreasing work commitment into adulthood (P < 0.001). Using linear regression models for panel data, an association with continued use of cannabis across the life-course and a lowering of work commitment was established. Results remained significant even when controlling for a range of other factors known to be related to work commitment, such as socio-economic background, education, labour market experiences, mental health and family characteristics (P < 0.05).   In Norway the use of

Frontal lobe dysfunction in long-term cannabis users.

PubMed

Lundqvist, T; Jönsson, S; Warkentin, S

2001-01-01

This study examined the neurophysiological effects of cannabis. Cerebral blood flow (CBF) was measured in 12 long-term cannabis users shortly after cessation of cannabis use (mean 1.6 days). The findings showed significantly lower mean hemispheric blood flow values and significantly lower frontal values in the cannabis subjects compared to normal controls. The results suggest that the functional level of the frontal lobes is affected by long-term cannabis use.

Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects

PubMed Central

Russo, Ethan B

2011-01-01

Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL−1. They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant. LINKED ARTICLES

Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.

PubMed

Russo, Ethan B

2011-08-01

Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL(-1) . They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant. http

Measuring cannabis consumption: Psychometric properties of the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU)

PubMed Central