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.

Effects of Cannabis sativa extract on haloperidol-induced catalepsy and oxidative stress in the mice

PubMed Central

Abdel-Salam, Omar M.E.; El-Sayed El-Shamarka, Marawa; Salem, Neveen A.; El-Din M. Gaafar, Alaa

2012-01-01

Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms due to blockade of dopamine D2 receptors in the striatum. Interest in medicinal uses of cannabis is growing. Cannabis sativa has been suggested as a possible adjunctive in treatment of Parkinson's disease. The present study aimed to investigate the effect of repeated administration of an extract of Cannabis sativa on catalepsy and brain oxidative stress induced by haloperidol administration in mice. Cannabis extract was given by subcutaneous route at 5, 10 or 20 mg/kg (expressed as Δ9-tetrahydrocannabinol) once daily for 18 days and the effect on haloperidol (1 mg/kg, i.p.)-induced catalepsy was examined at selected time intervals using the bar test. Mice were euthanized 18 days after starting cannabis injection when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (the concentrations of nitrite/nitrate) were determined in brain and liver. In saline-treated mice, no catalepsy was observed at doses of cannabis up to 20 mg/kg. Mice treated with haloperidol at the dose of 1 mg/kg, exhibited significant cataleptic response. Mice treated with cannabis and haloperidol showed significant decrease in catalepsy duration, compared with the haloperidol only treated group. This decrease in catalepsy duration was evident on days 1-12 after starting cannabis injection. Later the effect of cannabis was not apparent. The administration of only cannabis (10 or 20 mg/kg) decreased brain MDA by 17.5 and 21.8 %, respectively. The level of nitric oxide decreased by 18 % after cannabis at 20 mg/kg. Glucose in brain decreased by 20.1 % after 20 mg/kg of cannabis extract. The administration of only haloperidol increased MDA (22.2 %), decreased GSH (25.7 %) and increased brain nitric oxide by 44.1 %. The administration of cannabis (10 or 20 mg/kg) to haloperidol-treated mice resulted in a significant decrease in brain MDA and nitric

Effects of Cannabis sativa extract on haloperidol-induced catalepsy and oxidative stress in the mice.

PubMed

Abdel-Salam, Omar M E; El-Sayed El-Shamarka, Marawa; Salem, Neveen A; El-Din M Gaafar, Alaa

2012-01-01

Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms due to blockade of dopamine D2 receptors in the striatum. Interest in medicinal uses of cannabis is growing. Cannabis sativa has been suggested as a possible adjunctive in treatment of Parkinson's disease. The present study aimed to investigate the effect of repeated administration of an extract of Cannabis sativa on catalepsy and brain oxidative stress induced by haloperidol administration in mice. Cannabis extract was given by subcutaneous route at 5, 10 or 20 mg/kg (expressed as Δ(9)-tetrahydrocannabinol) once daily for 18 days and the effect on haloperidol (1 mg/kg, i.p.)-induced catalepsy was examined at selected time intervals using the bar test. Mice were euthanized 18 days after starting cannabis injection when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (the concentrations of nitrite/nitrate) were determined in brain and liver. In saline-treated mice, no catalepsy was observed at doses of cannabis up to 20 mg/kg. Mice treated with haloperidol at the dose of 1 mg/kg, exhibited significant cataleptic response. Mice treated with cannabis and haloperidol showed significant decrease in catalepsy duration, compared with the haloperidol only treated group. This decrease in catalepsy duration was evident on days 1-12 after starting cannabis injection. Later the effect of cannabis was not apparent. The administration of only cannabis (10 or 20 mg/kg) decreased brain MDA by 17.5 and 21.8 %, respectively. The level of nitric oxide decreased by 18 % after cannabis at 20 mg/kg. Glucose in brain decreased by 20.1 % after 20 mg/kg of cannabis extract. The administration of only haloperidol increased MDA (22.2 %), decreased GSH (25.7 %) and increased brain nitric oxide by 44.1 %. The administration of cannabis (10 or 20 mg/kg) to haloperidol-treated mice resulted in a significant decrease in brain MDA and nitric

Detection and Quantification of Cannabinoids in Extracts of Cannabis sativa Roots Using LC-MS/MS.

PubMed

Gul, Waseem; Gul, Shahbaz W; Chandra, Suman; Lata, Hemant; Ibrahim, Elsayed A; ElSohly, Mahmoud A

2018-03-01

A liquid chromatography-tandem mass spectrometry single-laboratory validation was performed for the detection and quantification of the 10 major cannabinoids of cannabis, namely, (-)- trans -Δ 9 -tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, tetrahydrocannabivarian, cannabinol, (-)- trans -Δ 8 -tetrahydrocannabinol, cannabidiolic acid, cannabigerolic acid, and Δ 9 -tetrahydrocannabinolic acid-A, in the root extract of Cannabis sativa . Acetonitrile : methanol (80 : 20, v/v) was used for extraction; d 3 -cannabidiol and d 3 - tetrahydrocannabinol were used as the internal standards. All 10 cannabinoids showed a good regression relationship with r 2  > 0.99. The validated method is simple, sensitive, and reproducible and is therefore suitable for the detection and quantification of these cannabinoids in extracts of cannabis roots. To our knowledge, this is the first report for the quantification of cannabinoids in cannabis roots. Georg Thieme Verlag KG Stuttgart · New York.

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.

First systematic evaluation of the potency of Cannabis sativa plants grown in Albania.

PubMed

Bruci, Zana; Papoutsis, Ioannis; Athanaselis, Sotirios; Nikolaou, Panagiota; Pazari, Ermira; Spiliopoulou, Chara; Vyshka, Gentian

2012-10-10

Cannabis products (marijuana, hashish, cannabis oil) are the most frequently abused illegal substances worldwide. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of Cannabis sativa plant, whereas cannabidiol (CBD) and cannabinol (CBN) are other major but no psychoactive constituents. Many studies have already been carried out on these compounds and chemical research was encouraged due to the legal implications concerning the misuse of marijuana. The aim of this study was to determine THC, CBD and CBN in a significant number of cannabis samples of Albanian origin, where cannabis is the most frequently used drug of abuse, in order to evaluate and classify them according to their cannabinoid composition. A GC-MS method was used, in order to assay cannabinoid content of hemp samples harvested at different maturation degree levels during the summer months and grown in different areas of Albania. This method can also be used for the determination of plant phenotype, the evaluation of psychoactive potency and the control of material quality. The highest cannabinoid concentrations were found in the flowers of cannabis. The THC concentrations in different locations of Albania ranged from 1.07 to 12.13%. The influence of environmental conditions on cannabinoid content is discussed. The cannabinoid content of cannabis plants were used for their profiling, and it was used for their classification, according to their geographical origin. The determined concentrations justify the fact that Albania is an area where cannabis is extensively cultivated for illegal purposes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

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.

The safety and efficacy of 3% Cannabis seeds extract cream for reduction of human cheek skin sebum and erythema content.

PubMed

Ali, Atif; Akhtar, Naveed

2015-07-01

Escalated sebum fabrication is seen with an unattractive look and adds to the growth of acne. We aimed to investigate the efficacy and safety of 3% Cannabis seeds extract cream on human cheek skin sebum and erythema content. For this purpose, base plus 3% Cannabis seeds extract and base (control) were prepared for single blinded and comparative study. Healthy males were instructed to apply the base plus 3% Cannabis seeds extract and base twice a day to their cheeks for 12 weeks. Adverse events were observed to determine skin irritation. Measurements for sebum and erythema content were recorded at baseline, 2nd, 4th, 6th, 8th, 10th and 12th week in a control room with Sebumeter and Mexameter. Base plus 3% Cannabis seeds extract was found to be safe in volunteers. Measurements demonstrated that skin sebum and erythema content of base plus 3% Cannabis seeds extract treated side showed significant decrease (p<0.05) compared with base treated side. Base plus 3% Cannabis seeds extract showed safety. It was well tolerated for the reduction of skin sebum and erythema content. Its improved efficacy could be suggested for treatment of acne vulgaris, seborrhea, papules and pustules to get attractive facial appearance.

Cannabis, a complex plant: different compounds and different effects on individuals

PubMed Central

2012-01-01

Cannabis is a complex plant, with major compounds such as delta-9-tetrahydrocannabinol and cannabidiol, which have opposing effects. The discovery of its compounds has led to the further discovery of an important neurotransmitter system called the endocannabinoid system. This system is widely distributed in the brain and in the body, and is considered to be responsible for numerous significant functions. There has been a recent and consistent worldwide increase in cannabis potency, with increasing associated health concerns. A number of epidemiological research projects have shown links between dose-related cannabis use and an increased risk of development of an enduring psychotic illness. However, it is also known that not everyone who uses cannabis is affected adversely in the same way. What makes someone more susceptible to its negative effects is not yet known, however there are some emerging vulnerability factors, ranging from certain genes to personality characteristics. In this article we first provide an overview of the biochemical basis of cannabis research by examining the different effects of the two main compounds of the plant and the endocannabinoid system, and then go on to review available information on the possible factors explaining variation of its effects upon different individuals. PMID:23983983

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.

[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.

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.

Acute effects of Delta9-tetrahydrocannabinol and standardized cannabis extract on the auditory evoked mismatch negativity.

PubMed

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

2007-12-01

Reduced amplitudes of auditory evoked mismatch negativity (MMN) have often been found in schizophrenic patients, indicating deficient auditory information processing and working memory. Cannabis-induced psychotic states may resemble schizophrenia. Currently, there are discussions focusing on the close relationship between cannabis, the endocannabinoid and dopaminergic system, and the onset of schizophrenic psychosis. This study investigated the effects of cannabis on MMN amplitude in 22 healthy volunteers (age 28+/-6 years, 11 male) by comparing Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and standardized cannabis extract containing Delta(9)-THC and cannabidiol (CBD) in a prospective, double-blind, placebo-controlled cross-over design. The MMNs resulting from 1000 auditory stimuli were recorded by 32 channel EEG. The standard stimuli were 1000 Hz, 80 dB SPL, and 100 ms duration. The deviant stimuli differed in frequency (1500 Hz). Significantly greater MMN amplitude values at central electrodes were found under cannabis extract, but not under Delta(9)-THC. There were no significant differences between MMN amplitudes at frontal electrodes. MMN amplitudes at central electrodes were significantly correlated with 11-OH-THC concentration, the most important psychoactive metabolite of Delta(9)-THC. Since the main difference between Delta(9)-THC and standardized cannabis extract is CBD, which seems to have neuroprotective and anti-psychotic properties, it can be speculated whether the greater MMN amplitude that may imply higher cortical activation and cognitive performance is related to the positive effects of CBD. This effect may be relevant for auditory cortex activity in particular because only MMN amplitudes at the central, but not at the frontal electrodes were enhanced under cannabis.

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...

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.

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®.

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.

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.

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.

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.

[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.

Lack of analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteers.

PubMed

Kraft, Birgit; Frickey, Nathalie A; Kaufmann, Rainer M; Reif, Marcus; Frey, Richard; Gustorff, Burkhard; Kress, Hans G

2008-07-01

Cannabinoid-induced analgesia was shown in animal studies of acute inflammatory and neuropathic pain. In humans, controlled clinical trials with Delta-tetrahydrocannabinol or other cannabinoids demonstrated analgesic efficacy in chronic pain syndromes, whereas the data in acute pain were less conclusive. Therefore, the aim of this study was to investigate the effects of oral cannabis extract in two different human models of acute inflammatory pain and hyperalgesia. The authors conducted a double-blind, crossover study in 18 healthy female volunteers. Capsules containing Delta-tetrahydrocannabinol-standardized cannabis extract or active placebo were orally administered. A circular sunburn spot was induced at one upper leg. Heat and electrical pain thresholds were determined at the erythema, the area of secondary hyperalgesia, and the contralateral leg. Intradermal capsaicin-evoked pain and areas of flare and secondary hyperalgesia were measured. Primary outcome parameters were heat pain thresholds in the sunburn erythema and the capsaicin-evoked area of secondary hyperalgesia. Secondary measures were electrical pain thresholds, sunburn-induced secondary hyperalgesia, and capsaicin-induced pain. Cannabis extract did not affect heat pain thresholds in the sunburn model. Electrical thresholds (250 Hz) were significantly lower compared with baseline and placebo. In the capsaicin model, the area of secondary hyperalgesia, flare, and spontaneous pain were not altered. To conclude, no analgesic or antihyperalgesic activity of cannabis extract was found in the experiments. Moreover, the results even point to the development of a hyperalgesic state under cannabinoids. Together with previous data, the current results suggest that cannabinoids are not effective analgesics for the treatment of acute nociceptive pain in humans.

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.

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.

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.

Standardized Cannabis sativa extract attenuates tau and stathmin gene expression in the melanoma cell line.

PubMed

Vaseghi, Golnaz; Taki, Mohamad Javad; Javanmard, Shaghayegh Haghjooy

2017-10-01

Metastasis is the main cause of death in patients with melanoma. Cannabis-based medicines are effective adjunctive drugs in cancer patients. Tau and Stathmin proteins are the key proteins in cancer metastasis. Here we have investigated the effect of a standardized Cannabis sativa extract on cell migration and Tau and Stathmin gene expression in the melanoma cell line. In the treatment group, melanoma (B1617) was treated 48 hr with various concentrations of standardized C. sativa extract. Cells with no treatment were considered as the control group, then study was followed by Quantitative RT-Real Time PCR assay. Relative gene expression was calculated by the ΔΔct method. Migration assay was used to evaluate cancer metastasis. Tau and stathmin gene expression was significantly decreased compared to the control group. Cell migration was also significantly reduced compared to controls. C. sativa decreased tau and stathmin gene expression and cancer metastasis. The results may have some clinical relevance for the use of cannabis-based medicines in patients with metastatic melanoma.

Cloud point extraction of Δ9-tetrahydrocannabinol from cannabis resin.

PubMed

Ameur, S; Haddou, B; Derriche, Z; Canselier, J P; Gourdon, C

2013-04-01

A cloud point extraction coupled with high performance liquid chromatography (HPLC/UV) method was developed for the determination of Δ(9)-tetrahydrocannabinol (THC) in micellar phase. The nonionic surfactant "Dowfax 20B102" was used to extract and pre-concentrate THC from cannabis resin, prior to its determination with a HPLC-UV system (diode array detector) with isocratic elution. The parameters and variables affecting the extraction were investigated. Under optimum conditions (1 wt.% Dowfax 20B102, 1 wt.% Na2SO4, T = 318 K, t = 30 min), this method yielded a quite satisfactory recovery rate (~81 %). The limit of detection was 0.04 μg mL(-1), and the relative standard deviation was less than 2 %. Compared with conventional solid-liquid extraction, this new method avoids the use of volatile organic solvents, therefore is environmentally safer.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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

A novel component of cannabis extract potentiates excitatory synaptic transmission in rat olfactory cortex in vitro.

PubMed

Whalley, Benjamin J; Wilkinson, Jonathan D; Williamson, Elizabeth M; Constanti, Andrew

2004-07-15

Cannabis is a potential treatment for epilepsy, although the few human studies supporting this use have proved inconclusive. Previously, we showed that a standardized cannabis extract (SCE), isolated Delta9-tetrahydrocannabinol (Delta9-THC), and even Delta9-THC-free SCE inhibited muscarinic agonist-induced epileptiform bursting in rat olfactory cortical brain slices, acting via CB1 receptors. The present work demonstrates that although Delta9-THC (1 microM) significantly depressed evoked depolarizing postsynaptic potentials (PSPs) in rat olfactory cortex neurones, both SCE and Delta9-THC-free SCE significantly potentiated evoked PSPs (all results were fully reversed by the CB1 receptor antagonist SR141716A, 1 microM); interestingly, the potentiation by Delta9-THC-free SCE was greater than that produced by SCE. On comparing the effects of Delta9-THC-free SCE upon evoked PSPs and artificial PSPs (aPSPs; evoked electrotonically following brief intracellular current injection), PSPs were enhanced, whereas aPSPs were unaffected, suggesting that the effect was not due to changes in background input resistance. Similar recordings made using CB1 receptor-deficient knockout mice (CB1-/-) and wild-type littermate controls revealed cannabinoid or extract-induced changes in membrane resistance, cell excitability and synaptic transmission in wild-type mice that were similar to those seen in rat neurones, but no effect on these properties were seen in CB1-/- cells. It appears that the unknown extract constituent(s) effects over-rode the suppressive effects of Delta9-THC on excitatory neurotransmitter release, which may explain some patients' preference for herbal cannabis rather than isolated Delta9-THC (due to attenuation of some of the central Delta9-THC side effects) and possibly account for the rare incidence of seizures in some individuals taking cannabis recreationally.

When and How to Treat Possible Cannabis Use Disorder.

PubMed

Lévesque, Annie; Le Foll, Bernard

2018-07-01

Cannabis (marijuana) is a drug product derived from the plant Cannabis sativa. Cannabinoid is a general term for all chemical constituents of the cannabis plant. Legalization of marijuana in numerous US states, the availability of cannabis of higher potency, and the emergence of synthetic cannabinoids may have contributed to increased demand for related medical services. The most effective available treatments for cannabis use disorder are psychosocial approaches. There is no pharmacotherapy approved treatment. This article reviews the current state of knowledge regarding effective treatments for cannabis use disorder. Copyright © 2018 Elsevier Inc. All rights reserved.

Characteristics of cannabinoids composition of Cannabis plants grown in Northern Thailand and its forensic application.

PubMed

Tipparat, Prapatsorn; Natakankitkul, Surapol; Chamnivikaipong, Pipop; Chutiwat, Sirot

2012-02-10

The Thai government has recognized the possibility for legitimate cultivation of hemp. Further study of certain cannabinoid characteristics is necessary in establishing criteria for regulation of cannabis cultivation in Thailand. For this purpose, factors affecting characteristics of cannabinoids composition of Thai-grown cannabis were investigated. Plants were cultivated from seeds derived from the previous studies under the same conditions. 372 cannabis samples from landraces, three different trial fields and seized marijuana were collected. 100g of each sample was dried, ground and quantitatively analyzed for THC, CBD and CBN contents by GC-FID. The results showed that cannabis grown during March-June which had longer vegetative stages and longer photoperiod exposure, had higher cannabinoids contents than those grown in August. The male plants grown in trial fields had the range of THC contents from 0.722% to 0.848% d.w. and average THC/CBD ratio of 1.9. Cannabis in landraces at traditional harvest time of 75 days had a range of THC contents from 0.874% to 1.480% d.w. and an average THC/CBD ratio of 2.6. The THC contents and THC/CBD ratios of cannabis in second generation crops grown in the same growing season were found to be lower than those grown in the first generation, unless fairly high temperatures and a lesser amount of rainfall were present. The average THC content in seized fresh marijuana was 2.068% d.w. while THC/CBD ratios were between 12.6 and 84.09, which is 10-45 times greater than those of similar studied cannabis samples from the previous study. However, most Thai cannabis in landraces and in trial fields giving a low log(10) value of THC/CBD ratio at below 1 may be classified as intermediate type, whereas seized marijuana giving a higher log(10) value at above 1 could be classified as drug type. Therefore, the expanded information provided by the current study will assist in the development of criteria for regulation of hemp cultivation in

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

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.

Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides.

PubMed

Gagne, Steve J; Stout, Jake M; Liu, Enwu; Boubakir, Zakia; Clark, Shawn M; Page, Jonathan E

2012-07-31

Δ(9)-Tetrahydrocannabinol (THC) and other cannabinoids are responsible for the psychoactive and medicinal properties of Cannabis sativa L. (marijuana). The first intermediate in the cannabinoid biosynthetic pathway is proposed to be olivetolic acid (OA), an alkylresorcinolic acid that forms the polyketide nucleus of the cannabinoids. OA has been postulated to be synthesized by a type III polyketide synthase (PKS) enzyme, but so far type III PKSs from cannabis have been shown to produce catalytic byproducts instead of OA. We analyzed the transcriptome of glandular trichomes from female cannabis flowers, which are the primary site of cannabinoid biosynthesis, and searched for polyketide cyclase-like enzymes that could assist in OA cyclization. Here, we show that a type III PKS (tetraketide synthase) from cannabis trichomes requires the presence of a polyketide cyclase enzyme, olivetolic acid cyclase (OAC), which catalyzes a C2-C7 intramolecular aldol condensation with carboxylate retention to form OA. OAC is a dimeric α+β barrel (DABB) protein that is structurally similar to polyketide cyclases from Streptomyces species. OAC transcript is present at high levels in glandular trichomes, an expression profile that parallels other cannabinoid pathway enzymes. Our identification of OAC both clarifies the cannabinoid pathway and demonstrates unexpected evolutionary parallels between polyketide biosynthesis in plants and bacteria. In addition, the widespread occurrence of DABB proteins in plants suggests that polyketide cyclases may play an overlooked role in generating plant chemical diversity.

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

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.

Psychomotor performance in relation to acute oral administration of Delta9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects.

PubMed

Roser, Patrik; Gallinat, Jürgen; Weinberg, Gordon; Juckel, Georg; Gorynia, Inge; Stadelmann, Andreas M

2009-08-01

Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users. The high levels of central cannabinoid (CB(1)) receptors in the basal ganglia, the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity. Based on the close relationship between cannabis use, the endogenous cannabinoid system and motor disturbances found in schizophrenia, we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-handed volunteers (age 27.9 +/- 2.9 years, 12 male) by comparing Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and standardized cannabis extract containing Delta(9)-THC and cannabidiol. Psychomotor performance was assessed by using a finger tapping test series. Cannabis extract, but not Delta(9)-THC, revealed a significant reduction of right-hand tapping frequencies that was also found in schizophrenia. As to the pure Delta(9)-THC condition, left-hand tapping frequencies were correlated with the plasma concentrations of the Delta(9)-THC metabolite 11-OH-THC. These effects are thought to be related to cannabinoid actions on CB(1) receptors in the basal ganglia, the cerebral cortex and the cerebellum. Our data further demonstrate that acute CB(1) receptor activation under the cannabis extract condition may also affect intermanual coordination (IMC) as an index of interhemispheric transfer. AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve. This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum.

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.

Yield of illicit indoor cannabis cultivation in the Netherlands.

PubMed

Toonen, Marcel; Ribot, Simon; Thissen, Jac

2006-09-01

To obtain a reliable estimation on the yield of illicit indoor cannabis cultivation in The Netherlands, cannabis plants confiscated by the police were used to determine the yield of dried female flower buds. The developmental stage of flower buds of the seized plants was described on a scale from 1 to 10 where the value of 10 indicates a fully developed flower bud ready for harvesting. Using eight additional characteristics describing the grow room and cultivation parameters, regression analysis with subset selection was carried out to develop two models for the yield of indoor cannabis cultivation. The median Dutch illicit grow room consists of 259 cannabis plants, has a plant density of 15 plants/m(2), and 510 W of growth lamps per m(2). For the median Dutch grow room, the predicted yield of female flower buds at the harvestable developmental stage (stage 10) was 33.7 g/plant or 505 g/m(2).

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

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.

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.

New food allergies in a European non-Mediterranean region: is Cannabis sativa to blame?

PubMed

Ebo, D G; Swerts, S; Sabato, V; Hagendorens, M M; Bridts, C H; Jorens, P G; De Clerck, L S

2013-01-01

Allergy to fruit and vegetables exhibit geographic variation regarding the severity of symptoms and depending on the sensitization profile of the patient. These sensitization profiles and routes remain incompletely understood. Cannabis is a very popular drug and derived from Cannabis sativa, a plant containing lipid transfer proteins (LTP) also known as important allergens in plant and fruit allergies. In this study we sought to elucidate a potential connection between C. sativa allergy and plant food allergies. A case-control study involving 21 patients consulting for plant food allergies. Twelve patients were cannabis allergic and 9 had a pollen or latex allergy without cannabis allergy. Testing for cannabis IgE implied measurement of specific IgE, skin testing and basophil activation tests. Allergen component analysis was performed with a microarray technique. Plant food allergy in patients with documented cannabis allergy had more severe reactions than patients without cannabis allergy and frequently implied fruits and vegetables that are not observed in a (birch) pollen-related food syndrome. With the exception of 1 patient with cannabis allergy, all were sensitized to nonspecific (ns)-LTP. Our data suggest that illicit cannabis abuse can result in cannabis allergy with sensitization to ns-LTP. This sensitization might result in various plant-food allergies. Additional collaborative studies in different geographical areas are needed to further elucidate on this hypothesis. Copyright © 2013 S. Karger AG, Basel.

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

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.

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 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.

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.

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.

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

Evolution of the content of THC and other major cannabinoids in drug-type cannabis cuttings and seedlings during growth of plants.

PubMed

De Backer, Benjamin; Maebe, Kevin; Verstraete, Alain G; Charlier, Corinne

2012-07-01

In Europe, authorities frequently ask forensic laboratories to analyze seized cannabis plants to prove that cultivation was illegal (drug type and not fiber type). This is generally done with mature and flowering plants. However, authorities are often confronted with very young specimens. The aim of our study was to evaluate when the chemotype of cannabis plantlets can be surely determined through analysis of eight major cannabinoids content during growth. Drug-type seedlings and cuttings were cultivated, sampled each week, and analyzed by high-performance liquid chromatography with diode array detection. The chemotype of clones was recognizable at any developmental stage because of high total Δ(9)-tetrahydrocannabinol (THC) concentrations even at the start of the cultivation. Conversely, right after germination seedlings contained a low total THC content, but it increased quickly with plant age up, allowing chemotype determination after 3 weeks. In conclusion, it is not necessary to wait for plants' flowering to identify drug-type cannabis generally cultivated in Europe. © 2012 American Academy of Forensic Sciences.

Cannabis in Pain Treatment: Clinical and Research Considerations.

PubMed

Savage, Seddon R; Romero-Sandoval, Alfonso; Schatman, Michael; Wallace, Mark; Fanciullo, Gilbert; McCarberg, Bill; Ware, Mark

2016-06-01

Cannabinoids show promise as therapeutic agents, particularly as analgesics, but their development and clinical use has been complicated by recognition of their botanical source, cannabis, as a substance of misuse. Although research into endogenous cannabinoid systems and potential cannabinoid pharmaceuticals is slowly increasing, there has been intense societal interest in making herbal (plant) cannabis available for medicinal use; 23 U.S. States and all Canadian provinces currently permit use in some clinical contexts. Whether or not individual professionals support the clinical use of herbal cannabis, all clinicians will encounter patients who elect to use it and therefore need to be prepared to advise them on cannabis-related clinical issues despite limited evidence to guide care. Expanded research on cannabis is needed to better determine the individual and public health effects of increasing use of herbal cannabis and to advance understanding of the pharmaceutical potential of cannabinoids as medications. This article reviews clinical, research, and policy issues related to herbal cannabis to support clinicians in thoughtfully advising and caring for patients who use cannabis, and it examines obstacles and opportunities to expand research on the health effects of herbal cannabis and cannabinoids. Herbal cannabis is increasingly available for clinical use in the United States despite continuing controversies over its efficacy and safety. This article explores important considerations in the use of plant Cannabis to better prepare clinicians to care for patients who use it, and identifies needed directions for research. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

In silico gene expression profiling in Cannabis sativa.

PubMed

Massimino, Luca

2017-01-01

The cannabis plant and its active ingredients (i.e., cannabinoids and terpenoids) have been socially stigmatized for half a century. Luckily, with more than 430,000 published scientific papers and about 600 ongoing and completed clinical trials, nowadays cannabis is employed for the treatment of many different medical conditions. Nevertheless, even if a large amount of high-throughput functional genomic data exists, most researchers feature a strong background in molecular biology but lack advanced bioinformatics skills. In this work, publicly available gene expression datasets have been analyzed giving rise to a total of 40,224 gene expression profiles taken from cannabis plant tissue at different developmental stages. The resource presented here will provide researchers with a starting point for future investigations with Cannabis sativa .

Therapeutic potential of cannabis-related drugs.

PubMed

Alexander, Stephen P H

2016-01-04

In this review, I will consider the dual nature of Cannabis and cannabinoids. The duality arises from the potential and actuality of cannabinoids in the laboratory and clinic and the 'abuse' of Cannabis outside the clinic. The therapeutic areas currently best associated with exploitation of Cannabis-related medicines include pain, epilepsy, feeding disorders, multiple sclerosis and glaucoma. As with every other medicinal drug of course, the 'trick' will be to maximise the benefit and minimise the cost. After millennia of proximity and exploitation of the Cannabis plant, we are still playing catch up with an understanding of its potential influence for medicinal benefit. Copyright © 2015 Elsevier Inc. All rights reserved.

Cannabis sativa: The Plant of the Thousand and One Molecules

PubMed Central

Andre, Christelle M.; Hausman, Jean-Francois; Guerriero, Gea

2016-01-01

Cannabis sativa L. is an important herbaceous species originating from Central Asia, which has been used in folk medicine and as a source of textile fiber since the dawn of times. This fast-growing plant has recently seen a resurgence of interest because of its multi-purpose applications: it is indeed a treasure trove of phytochemicals and a rich source of both cellulosic and woody fibers. Equally highly interested in this plant are the pharmaceutical and construction sectors, since its metabolites show potent bioactivities on human health and its outer and inner stem tissues can be used to make bioplastics and concrete-like material, respectively. In this review, the rich spectrum of hemp phytochemicals is discussed by putting a special emphasis on molecules of industrial interest, including cannabinoids, terpenes and phenolic compounds, and their biosynthetic routes. Cannabinoids represent the most studied group of compounds, mainly due to their wide range of pharmaceutical effects in humans, including psychotropic activities. The therapeutic and commercial interests of some terpenes and phenolic compounds, and in particular stilbenoids and lignans, are also highlighted in view of the most recent literature data. Biotechnological avenues to enhance the production and bioactivity of hemp secondary metabolites are proposed by discussing the power of plant genetic engineering and tissue culture. In particular two systems are reviewed, i.e., cell suspension and hairy root cultures. Additionally, an entire section is devoted to hemp trichomes, in the light of their importance as phytochemical factories. Ultimately, prospects on the benefits linked to the use of the -omics technologies, such as metabolomics and transcriptomics to speed up the identification and the large-scale production of lead agents from bioengineered Cannabis cell culture, are presented. PMID:26870049

In silico discovery of terpenoid metabolism in Cannabis sativa.

PubMed

Massimino, Luca

2017-01-01

Due to their efficacy, cannabis based therapies are currently being prescribed for the treatment of many different medical conditions. Interestingly, treatments based on the use of cannabis flowers or their derivatives have been shown to be very effective, while therapies based on drugs containing THC alone lack therapeutic value and lead to increased side effects, likely resulting from the absence of other pivotal entourage compounds found in the Phyto-complex. Among these compounds are terpenoids, which are not produced exclusively by cannabis plants, so other plant species must share many of the enzymes involved in their metabolism. In the present work, 23,630 transcripts from the canSat3 reference transcriptome were scanned for evolutionarily conserved protein domains and annotated in accordance with their predicted molecular functions. A total of 215 evolutionarily conserved genes encoding enzymes presumably involved in terpenoid metabolism are described, together with their expression profiles in different cannabis plant tissues at different developmental stages. The resource presented here will aid future investigations on terpenoid metabolism in Cannabis sativa .

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.

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.

[Characteristics of Cannabis sativa L.: seed morphology, germination and growth characteristics, and distinction from Hibiscus cannabinus L].

PubMed

Yoshimatsu, Kayo; Kitazawa, Takashi; Kawano, Noriaki; Iida, Osamu; Kawahara, Nobuo

2010-02-01

Illegal cannabis (Cannabis sativa L.) cultivation is still a social problem worldwide. Fifty inquiries on cannabis that Research Center for Medicinal Plant Resources (Tsukuba Division) received between January 1, 2000 and March 31, 2009 were itemized in to 8 categories; 1: seed identification, 2: plant identification, 3: indoor cultivation, 4: outdoor cultivation, 5: germination and growth characteristics, 6: expected amount of cannabis products derived from illegal cannabis plant, 7: non-narcotic cannabis and 8: usage of medicinal cannabis. Top three inquiries were 1: seed identification (16 cases), 3: indoor cultivation (10 cases) and 4: outdoor cultivation (6 cases). Characteristics of cannabis, namely seed morphology, germination and growth characteristics, and distinction from kenaf (Hibiscus cannabinus L.) that is frequently misjudged as cannabis, were studied to contribute for prevention of illegal cannabis cultivation.

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.

[Argentina enacts first law on medical use of the cannabis plant. History and perspectives].

PubMed

De Vito, Eduardo L

2017-01-01

In the last few years, great expectations have risen in the society concerning the eventual therapeutic usefulness of compounds derived from the cannabis plant. It is well known that these compounds are being used in treating certain health conditions, either through medical prescription or self-administration. Extreme opinions range from believing that it is a harmful and dangerous drug to sustaining that it is a panacea. However, the sheer existence of an endocannabinoid system in the brain compels us to study its dimensions and derivations thoroughly. It is expected that controversies and knowledge gaps will be clarified within the framework of this new law. Prohibitionism should not be a category of analysis. Regardless of the therapeutic effects of cannabinoid compounds, demonstrated or to be demonstrated, there are already severe restrictions on their use, which mirror the still existing restrictions to the use of opioids (drugs of definite utility but on which a huge taboo persists). This review presents the first Argentine law on the medical use of cannabis. Milestones in the history of marijuana at the national level are pointed out, which are inextricably linked to world trends either in favor or against prohibition. The current status of the use of cannabis oil in the country and evidences for its therapeutic value are also analyzed. Evidences on its therapeutic value are also analyzed as well as the current status of the use of cannabis oil in our country.

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.

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.

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.

Inhibitory effect of standardized cannabis sativa extract and its ingredient cannabidiol on rat and human bladder contractility.

PubMed

Capasso, Raffaele; Aviello, Gabriella; Borrelli, Francesca; Romano, Barbara; Ferro, Matteo; Castaldo, Luigi; Montanaro, Vittorino; Altieri, Vincenzo; Izzo, Angelo A

2011-04-01

To evaluate the effect of a Cannabis sativa extract enriched in cannabidiol (CBD) botanic drug substance (BDS) and pure CBD, on bladder contractility in vitro. Cannabis based-medicines, including CBD-enriched extracts, have been shown to reduce urinary urgency, incontinence episodes, frequency, and nocturia in patients with multiple sclerosis. Strips were cut from male Wistar rats and the human bladder body and placed in organ baths containing Krebs solution. Contractions were induced by electrical field stimulation, acetylcholine, KCl, and α,β-methylene adenosine triphosphate. CBD BDS significantly reduced the contractions induced by acetylcholine, but not those induced with electrical field stimulation, KCl, or α,β-methylene adenosine triphosphate in the isolated rat bladder. The inhibitory effect of CBD BDS was not significantly modified by the cannabinoid or opioid receptor antagonists or by modulators of calcium levels, but it was increased by ruthenium red and capsazepine, 2 transient receptor potential vanilloid type-1 blockers. In humans, CBD BDS and pure CBD significantly reduced acetylcholine-induced contractions, an effect that was not changed by the transient receptor potential vanilloid type-1 blockers. Our data have suggested that CBD BDS reduces cholinergic-mediated contractility and that this effect is modulated by transient receptor potential vanilloid type-1 in rats but not in humans. CBD is the chemical ingredient of CBD BDS responsible for such activity. If confirmed in vivo, such results could provide a pharmacologic basis to explain, at least in part, the efficacy of Cannabis medicines in reducing incontinence episodes in patients with multiple sclerosis. Copyright © 2011 Elsevier Inc. All rights reserved.

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

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.

[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.

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.

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: A Treasure Trove or Pandora's Box?

PubMed

Solymosi, Katalin; Köfalvi, Attila

2017-01-01

Cannabis is one of the earliest cultivated plants. Cannabis of industrial utility and culinary value is generally termed as hemp. Conversely, cannabis that is bred for medical, spiritual and recreational purposes is called marijuana. The female marijuana plant produces a significant quantity of bio- and psychoactive phytocannabinoids, which regained the spotlight with the discovery of the endocannabinoid system of the animals in the early 90's. Nevertheless, marijuana is surrounded by controversies, debates and misconceptions related to its taxonomic classification, forensic identification, medical potential, legalization and its long-term health consequences. In the first part, we provide an in-depth review of the botany and taxonomy of Cannabis. We then overview the biosynthesis of phytocannabinoids within the glandular trichomes with emphasis on the role of peculiar plastids in the production of the secreted material. We also compile the analytical methods used to determine the phytocannabinoid composition of glandular trichomes. In the second part, we revisit the psychobiology and molecular medicine of marijuana. We summarize our current knowledge on the recreational use of cannabis with respect to the modes of consumption, short-term effects, chronic health consequences and cannabis use disorder. Next, we overview the molecular targets of a dozen major and minor bioactive cannabinoids in the body. This helps us introduce the endocannabinoid system in an unprecedented detail: its up-todate molecular biology, pharmacology, physiology and medical significance, and beyond. In conclusion, we offer an unbiased survey about cannabis to help better weigh its medical value versus the associated risks. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Role of cannabis in digestive disorders.

PubMed

Goyal, Hemant; Singla, Umesh; Gupta, Urvashi; May, Elizabeth

2017-02-01

Cannabis sativa, a subspecies of the Cannabis plant, contains aromatic hydrocarbon compounds called cannabinoids. [INCREMENT]-Tetrahydrocannabinol is the most abundant cannabinoid and is the main psychotropic constituent. Cannabinoids activate two types of G-protein-coupled cannabinoid receptors: cannabinoid type 1 receptor and cannabinoid type 2 receptor. There has been ongoing interest and development in research to explore the therapeutic potential of cannabis. [INCREMENT]-Tetrahydrocannabinol exerts biological functions on the gastrointestinal (GI) tract. Cannabis has been used for the treatment of GI disorders such as abdominal pain and diarrhea. The endocannabinoid system (i.e. endogenous circulating cannabinoids) performs protective activities in the GI tract and presents a promising therapeutic target against various GI conditions such as inflammatory bowel disease (especially Crohn's disease), irritable bowel syndrome, and secretion and motility-related disorders. The present review sheds light on the role of cannabis in the gut, liver, and pancreas and also on other GI symptoms, such as nausea and vomiting, cannabinoid hyperemesis syndrome, anorexia, weight loss, and chronic abdominal pain. Although the current literature supports the use of marijuana for the treatment of digestive disorders, the clinical efficacy of cannabis and its constituents for various GI disorders remains unclear.

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.

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.

The medical necessity for medicinal cannabis: prospective, observational study evaluating the treatment in cancer patients on supportive or palliative care.

PubMed

Bar-Sela, Gil; Vorobeichik, Marina; Drawsheh, Saher; Omer, Anat; Goldberg, Victoria; Muller, Ella

2013-01-01

Background. Cancer patients using cannabis report better influence from the plant extract than from synthetic products. However, almost all the research conducted to date has been performed with synthetic products. We followed patients with a medicinal cannabis license to evaluate the advantages and side effects of using cannabis by cancer patients. Methods. The study included two interviews based on questionnaires regarding symptoms and side effects, the first held on the day the license was issued and the second 6-8 weeks later. Cancer symptoms and cannabis side effects were documented on scales from 0 to 4 following the CTCAE. The distress thermometer was used also. Results. Of the 211 patients who had a first interview, only 131 had the second interview, 25 of whom stopped treatment after less than a week. All cancer or anticancer treatment-related symptoms showed significant improvement (P < 0.001). No significant side effects except for memory lessening in patients with prolonged cannabis use (P = 0.002) were noted. Conclusion. The positive effects of cannabis on various cancer-related symptoms are tempered by reliance on self-reporting for many of the variables. Although studies with a control group are missing, the improvement in symptoms should push the use of cannabis in palliative treatment of oncology patients.

The Medical Necessity for Medicinal Cannabis: Prospective, Observational Study Evaluating the Treatment in Cancer Patients on Supportive or Palliative Care

PubMed Central

Bar-Sela, Gil; Vorobeichik, Marina; Drawsheh, Saher; Omer, Anat; Goldberg, Victoria; Muller, Ella

2013-01-01

Background. Cancer patients using cannabis report better influence from the plant extract than from synthetic products. However, almost all the research conducted to date has been performed with synthetic products. We followed patients with a medicinal cannabis license to evaluate the advantages and side effects of using cannabis by cancer patients. Methods. The study included two interviews based on questionnaires regarding symptoms and side effects, the first held on the day the license was issued and the second 6–8 weeks later. Cancer symptoms and cannabis side effects were documented on scales from 0 to 4 following the CTCAE. The distress thermometer was used also. Results. Of the 211 patients who had a first interview, only 131 had the second interview, 25 of whom stopped treatment after less than a week. All cancer or anticancer treatment-related symptoms showed significant improvement (P < 0.001). No significant side effects except for memory lessening in patients with prolonged cannabis use (P = 0.002) were noted. Conclusion. The positive effects of cannabis on various cancer-related symptoms are tempered by reliance on self-reporting for many of the variables. Although studies with a control group are missing, the improvement in symptoms should push the use of cannabis in palliative treatment of oncology patients. PMID:23956774

What is the mechanism whereby cannabis use increases risk of psychosis?

PubMed

Luzi, Sonija; Morrison, Paul D; Powell, John; di Forti, Marta; Murray, Robin M

2008-10-01

Cannabis use has increased greatly over the last three decades. The various types of cannabis differ in their concentration of the main psychoactive component, Delta-9-tetrahydrocannabinol (THC), and the other major ingredient, cannabidiol (CBD). Plant engineering has maximized levels of THC, thus increasing the potency of street cannabis. It is well known that cannabis intoxication can cause brief psychotic symptoms like paranoia, whilst recent evidence demonstrates that heavy use of cannabis increases the risk of chronic psychoses like schizophrenia; genetic vulnerability seems to predispose some people to a higher risk. This paper starts to consider the neurochemical mechanisms whereby cannabis use increases the risk of psychosis.

THCVA-A - a new additional marker for illegal cannabis consumption.

PubMed

Radünz, Lars; Westphal, Folker; Maser, Edmund; Rochholz, Gertrud

2012-02-10

The aim of the present investigations was to find markers for differentiating between the consumption of illegal cannabis products and legal medication containing fully synthetic Δ9-tetrahydrocannabinol (Δ9-THC), e.g., Marinol capsules. Δ9-Tetrahydrocannabinolic acid A (Δ9-THCA-A) and Δ9-tetrahydrocannabivarinic acid A (Δ9-THCVA-A) were taken into consideration for analysis, because these substances are the precursors of Δ9-THC and Δ9-tetrahydrocannabivarin (Δ9-THCV) in plant material of Cannabis sativa and are not contained in medical THC formulations. Whereas Δ9-THCA-A is an already well investigated substance, there is little analytical data on Δ9-THCVA-A. The reason for the presented investigations was a case in which a man was tested positive for Δ9-THC during a routine traffic control claiming that the positive serum sample resulted from the intake of a THC medication (Marinol) and not from consuming illegal cannabis products. Sample preparation consisted of a protein precipitation with acetonitrile. Analysis was carried out on a Thermo Fisher LCQ Deca ion trap LC-MS-MS-system using electron spray ionization (ESI) in negative mode. MS(2)- and MS(3)-full scan spectra were recorded for Δ9-THCA-A and Δ9-THCVA-A starting from [M-H](-). Reference spectra were obtained by measuring a Δ9-THCA-A reference solution and an ethanolic cannabis extract for Δ9-THCVA-A as there is no reference material for this cannabinoid available on the market yet. Main transitions for Δ9-THCA-A were m/z 357→313 and 339 in the MS(2)-spectrum and m/z 313→245 and 191 in the MS(3)-spectrum. Fragmentation pattern of Δ9-THCVA-A was identical with a difference of 28 amu less for the precursor ion as well as the fragments due to a shorter alkyl side chain in the molecule (MS(2): m/z 329→285 and 311; MS(3): m/z 285→217 and 163). The two plant cannabinoids Δ9-THCA-A and Δ9-THCVA-A could be detected in the serum sample by LC-MS-MS which proved the intake of illegal

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.

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-based medicines for chronic neuropathic pain in adults.

PubMed

Mücke, Martin; Phillips, Tudor; Radbruch, Lukas; Petzke, Frank; Häuser, Winfried

2018-03-07

This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain. To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults. In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles. We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm. Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For

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)

Characterization of Cannabis sativa allergens.

PubMed

Nayak, Ajay P; Green, Brett J; Sussman, Gordon; Berlin, Noam; Lata, Hemant; Chandra, Suman; ElSohly, Mahmoud A; Hettick, Justin M; Beezhold, Donald H

2013-07-01

Allergic sensitization to Cannabis sativa is rarely reported, but the increasing consumption of marijuana has resulted in an increase in the number of individuals who become sensitized. To date, little is known about the causal allergens associated with C sativa. To characterize marijuana allergens in different components of the C sativa plant using serum IgE from marijuana sensitized patients. Serum samples from 23 patients with a positive skin prick test result to a crude C sativa extract were evaluated. IgE reactivity was variable between patients and C sativa extracts. IgE reactivity to C sativa proteins in Western blots was heterogeneous and ranged from 10 to 70 kDa. Putative allergens derived from 2-dimensional gels were identified. Prominent IgE reactive bands included a 23-kDa oxygen-evolving enhancer protein 2 and a 50-kDa protein identified to be the photosynthetic enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase. Additional proteins were identified in the proteomic analysis, including those from adenosine triphosphate synthase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and luminal binding protein (heat shock protein 70), suggesting these proteins are potential allergens. Deglycosylation studies helped refine protein allergen identification and demonstrated significant IgE antibodies against plant oligosaccharides that could help explain cross-reactivity. Identification and characterization of allergens from C sativa may be helpful in further understanding allergic sensitization to this plant species. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

Treatment of Crohn's disease with cannabis: an observational study.

PubMed

Naftali, Timna; Lev, Lihi Bar; Yablecovitch, Doron; Yablekovitz, Doron; Half, Elisabeth; Konikoff, Fred M

2011-08-01

The marijuana plant cannabis is known to have therapeutic effects, including improvement of inflammatory processes. However, no report of patients using cannabis for Crohn's disease (CD) was ever published. To describe the effects of cannabis use in patients suffering from CD. In this retrospective observational study we examined disease activity, use of medication, need for surgery, and hospitalization before and after cannabis use in 30 patients (26 males) with CD. Disease activity was assessed by the Harvey Bradshaw index for Crohn's disease. Of the 30 patients 21 improved significantly after treatment with cannabis. The average Harvey Bradshaw index improved from 14 +/- 6.7 to 7 +/- 4.7 (P < 0.001). The need for other medication was significantly reduced. Fifteen of the patients had 19 surgeries during an average period of 9 years before cannabis use, but only 2 required surgery during an average period of 3 years of cannabis use. This is the first report of cannabis use in Crohn's disease in humans. The results indicate that cannabis may have a positive effect on disease activity, as reflected by reduction in disease activity index and in the need for other drugs and surgery. Prospective placebo-controlled studies are warranted to fully evaluate the efficacy and side effects of cannabis in CD.

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.

Understanding Cultivar-Specificity and Soil Determinants of the Cannabis Microbiome

DOE PAGES

Winston, Max E.; Hampton-Marcell, Jarrad; Zarraonaindia, Iratxe; ...

2014-06-16

Understanding microbial partnerships with the medicinally and economically important crop Cannabis has the potential to affect agricultural practice by improving plant fitness and production yield. Furthermore, Cannabis presents an interesting model to explore plant-microbiome interactions as it produces numerous secondary metabolic compounds. Here we present the first description of the endorhiza-, rhizosphere-, and bulk soil-associated microbiome of five distinct Cannabis cultivars. Bacterial communities of the endorhiza showed significant cultivar-specificity. When controlling cultivar and soil type the microbial community structure was significantly different between plant cultivars, soil types, and between the endorhiza, rhizosphere and soil. In conclusion, the influence of soilmore » type, plant cultivar and sample type differentiation on the microbial community structure provides support for a previously published two-tier selection model, whereby community composition across sample types is determined mainly by soil type, while community structure within endorhiza samples is determined mainly by host cultivar.« less

Understanding Cultivar-Specificity and Soil Determinants of the Cannabis Microbiome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Winston, Max E.; Hampton-Marcell, Jarrad; Zarraonaindia, Iratxe

Understanding microbial partnerships with the medicinally and economically important crop Cannabis has the potential to affect agricultural practice by improving plant fitness and production yield. Furthermore, Cannabis presents an interesting model to explore plant-microbiome interactions as it produces numerous secondary metabolic compounds. Here we present the first description of the endorhiza-, rhizosphere-, and bulk soil-associated microbiome of five distinct Cannabis cultivars. Bacterial communities of the endorhiza showed significant cultivar-specificity. When controlling cultivar and soil type the microbial community structure was significantly different between plant cultivars, soil types, and between the endorhiza, rhizosphere and soil. In conclusion, the influence of soilmore » type, plant cultivar and sample type differentiation on the microbial community structure provides support for a previously published two-tier selection model, whereby community composition across sample types is determined mainly by soil type, while community structure within endorhiza samples is determined mainly by host cultivar.« less

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

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.

Evaluation of elemental profiling methods, including laser-induced breakdown spectroscopy (LIBS), for the differentiation of Cannabis plant material grown in different nutrient solutions.

PubMed

El-Deftar, Moteaa M; Robertson, James; Foster, Simon; Lennard, Chris

2015-06-01

Laser-induced breakdown spectroscopy (LIBS) is an emerging atomic emission based solid sampling technique that has many potential forensic applications. In this study, the analytical performance of LIBS, as well as that of inductively coupled plasma mass spectrometry (ICP-MS), laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and X-ray microfluorescence (μXRF), was evaluated for the ability to conduct elemental analyses on Cannabis plant material, with a specific investigation of the possible links between hydroponic nutrients and elemental profiles from associated plant material. No such study has been previously published in the literature. Good correlation among the four techniques was observed when the concentrations or peak areas of the elements of interest were monitored. For Cannabis samples collected at the same growth time, the elemental profiles could be related to the use of particular commercial nutrients. In addition, the study demonstrated that ICP-MS, LA-ICP-MS and LIBS are suitable techniques for the comparison of Cannabis samples from different sources, with high discriminating powers being achieved. On the other hand, μXRF method was not suitable for the discrimination of Cannabis samples originating from different growth nutrients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

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

PubMed

2003-01-01

GW Pharmaceuticals is undertaking a major research programme in the UK to develop and market distinct cannabis-based prescription medicines [THC:CBD, High THC, High CBD] in a range of medical conditions. The cannabis for this programme is grown in a secret location in the UK. It is expected that the product will be marketed in the US in late 2003. GW's cannabis-based products include selected phytocannabinoids from cannabis plants, including D9 tetrahydrocannabinol (THC) and cannabidiol (CBD). The company is investigating their use in three delivery systems, including sublingual spray, sublingual tablet and inhaled (but not smoked) dosage forms. The technology is protected by patent applications. Four different formulations are currently being investigated, including High THC, THC:CBD (narrow ratio), THC:CBD (broad ratio) and High CBD. GW is also developing a specialist security technology that will be incorporated in all its drug delivery systems. This technology allows for the recording and remote monitoring of patient usage to prevent any potential abuse of its cannabis-based medicines. GW plans to enter into agreements with other companies following phase III development, to secure the best commercialisation terms for its cannabis-based medicines. In June 2003, GW announced that exclusive commercialisation rights for the drug in the UK had been licensed to Bayer AG. The drug will be marketed under the Sativex brand name. This agreement also provides Bayer with an option to expand their license to include the European Union and certain world markets. GW was granted a clinical trial exemption certificate by the Medicines Control Agency to conduct clinical studies with cannabis-based medicines in the UK. The exemption includes investigations in the relief of pain of neurological origin and defects of neurological function in the following indications: multiple sclerosis (MS), spinal cord injury, peripheral nerve injury, central nervous system damage, neuroinvasive

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.

[Simultaneous Determination of Three Kinds of Effective Constituents in Cannabis Plants by Reversed-phase HPLC].

PubMed

Fu, Q; Shu, Z; Deng, K; Luo, X; Zeng, C G

2016-08-01

To establish a high performance liquid chromatographic （HPLC） method for simultaneous determination of three effective constituents, including tetrahydrocannabinol （THC）, cannabidiol （CBD） and cannabinol （CBN） in Cannabis plants. A C₁₈ column was used in this study, and acetonitrile-phosphate buffer （0.015 mol/L KH₂PO₄） was used as mobile phase at a flow rate of 1.0 mL/min. At a detection wavelength of 220 mm, UV absorption spectra were collected at the wavelength range of 190-400 nm, and the spectra and retention time were counted as qualitative evidence. THC, CBD and CBN could be well separated by this method. Three components had good linear relationship in the range of 0.4-40 μg/mL （ R ²≥0.999 3）. The recoveries were over 87%. The limits of detection were 1.8 ng, 2.0 ng and 1.3 ng, respectively. The relative standard deviation （RSD） were less than 5% for both inter-day and intra-day precisions. Reversed-phase HPLC method is simple, rapid and accurate, and it is suitable for the qualitative and quantitative detection of THC, CBD and CBN in Cannabis plants. Copyright© by the Editorial Department of Journal of Forensic Medicine

[Medical cannabis: the opportunity versus the temptation].

PubMed

Naftali, Timna

2011-12-01

The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea, and inflammation. Current research has shown cannabis to be a useful remedy for many diseases, including multiple sclerosis, dystonia, and chronic pain. Cannabinoids are used to improve food intake in anorexia of AIDS patients and to prevent vomiting due to cancer chemotherapy. In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and pain and diarrhea in Crohn's disease. Cannabinoids reduce the size of brain infarct and cardiac reperfusion injury. However, cannabinoid treatment is not free of side effects including euphoria, psychosis, anxiety, paranoia, dependence and abuse. Since the cannabinoid system is involved in many physiological and pathological processes, the therapeutic potential is great. We must not be blind to the opportunity offered to us by medical cannabis just because it is an illicit drug, nor should we be temped by the quick response of patients to the central effect of cannabis. More research is warranted to explore the full potential of cannabis as medicine.

The pharmacologic and clinical effects of medical cannabis.

PubMed

Borgelt, Laura M; Franson, Kari L; Nussbaum, Abraham M; Wang, George S

2013-02-01

Cannabis, or marijuana, has been used for medicinal purposes for many years. Several types of cannabinoid medicines are available in the United States and Canada. Dronabinol (schedule III), nabilone (schedule II), and nabiximols (not U.S. Food and Drug Administration approved) are cannabis-derived pharmaceuticals. Medical cannabis or medical marijuana, a leafy plant cultivated for the production of its leaves and flowering tops, is a schedule I drug, but patients obtain it through cannabis dispensaries and statewide programs. The effect that cannabinoid compounds have on the cannabinoid receptors (CB(1) and CB(2) ) found in the brain can create varying pharmacologic responses based on formulation and patient characteristics. The cannabinoid Δ(9) -tetrahydrocannabinol has been determined to have the primary psychoactive effects; the effects of several other key cannabinoid compounds have yet to be fully elucidated. Dronabinol and nabilone are indicated for the treatment of nausea and vomiting associated with cancer chemotherapy and of anorexia associated with weight loss in patients with acquired immune deficiency syndrome. However, pain and muscle spasms are the most common reasons that medical cannabis is being recommended. Studies of medical cannabis show significant improvement in various types of pain and muscle spasticity. Reported adverse effects are typically not serious, with the most common being dizziness. Safety concerns regarding cannabis include the increased risk of developing schizophrenia with adolescent use, impairments in memory and cognition, accidental pediatric ingestions, and lack of safety packaging for medical cannabis formulations. This article will describe the pharmacology of cannabis, effects of various dosage formulations, therapeutics benefits and risks of cannabis for pain and muscle spasm, and safety concerns of medical cannabis use. © 2013 Pharmacotherapy Publications, Inc.

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

Integrating cannabis into clinical cancer care.

PubMed

Abrams, D I

2016-03-01

Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use. However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use. For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression. Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite. Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy. A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia. Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis. Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating. Human studies should be conducted to address critical questions related to the foregoing effects.

Integrating cannabis into clinical cancer care

PubMed Central

Abrams, D.I.

2016-01-01

Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use. However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use. For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression. Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite. Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy. A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia. Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis. Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating. Human studies should be conducted to address critical questions related to the foregoing effects. PMID:27022315

Determination of Pesticide Residues in Cannabis Smoke

PubMed Central

Sullivan, Nicholas; Elzinga, Sytze; Raber, Jeffrey C.

2013-01-01

The present study was conducted in order to quantify to what extent cannabis consumers may be exposed to pesticide and other chemical residues through inhaled mainstream cannabis smoke. Three different smoking devices were evaluated in order to provide a generalized data set representative of pesticide exposures possible for medical cannabis users. Three different pesticides, bifenthrin, diazinon, and permethrin, along with the plant growth regulator paclobutrazol, which are readily available to cultivators in commercial products, were investigated in the experiment. Smoke generated from the smoking devices was condensed in tandem chilled gas traps and analyzed with gas chromatography-mass spectrometry (GC-MS). Recoveries of residues were as high as 69.5% depending on the device used and the component investigated, suggesting that the potential of pesticide and chemical residue exposures to cannabis users is substantial and may pose a significant toxicological threat in the absence of adequate regulatory frameworks. PMID:23737769

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

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.

Expression, purification and crystallization of a plant polyketide cyclase from Cannabis sativa

PubMed Central

Yang, Xinmei; Matsui, Takashi; Mori, Takahiro; Taura, Futoshi; Noguchi, Hiroshi; Abe, Ikuro; Morita, Hiroyuki

2015-01-01

Plant polyketides are a structurally diverse family of natural products. In the biosynthesis of plant polyketides, the construction of the carbocyclic scaffold is a key step in diversifying the polyketide structure. Olivetolic acid cyclase (OAC) from Cannabis sativa L. is the only known plant polyketide cyclase that catalyzes the C2–C7 intramolecular aldol cyclization of linear pentyl tetra-β-ketide-CoA to generate olivetolic acid in the biosynthesis of cannabinoids. The enzyme is also thought to belong to the dimeric α+β barrel (DABB) protein family. However, because of a lack of functional analysis of other plant DABB proteins and low sequence identity with the functionally distinct bacterial DABB proteins, the catalytic mechanism of OAC has remained unclear. To clarify the intimate catalytic mechanism of OAC, the enzyme was overexpressed in Escherichia coli and crystallized using the vapour-diffusion method. The crystals diffracted X-rays to 1.40 Å resolution and belonged to space group P3121 or P3221, with unit-cell parameters a = b = 47.3, c = 176.0 Å. Further crystallographic analysis will provide valuable insights into the structure–function relationship and catalytic mechanism of OAC. PMID:26625288

Expression, purification and crystallization of a plant polyketide cyclase from Cannabis sativa.

PubMed

Yang, Xinmei; Matsui, Takashi; Mori, Takahiro; Taura, Futoshi; Noguchi, Hiroshi; Abe, Ikuro; Morita, Hiroyuki

2015-12-01

Plant polyketides are a structurally diverse family of natural products. In the biosynthesis of plant polyketides, the construction of the carbocyclic scaffold is a key step in diversifying the polyketide structure. Olivetolic acid cyclase (OAC) from Cannabis sativa L. is the only known plant polyketide cyclase that catalyzes the C2-C7 intramolecular aldol cyclization of linear pentyl tetra-β-ketide-CoA to generate olivetolic acid in the biosynthesis of cannabinoids. The enzyme is also thought to belong to the dimeric α+β barrel (DABB) protein family. However, because of a lack of functional analysis of other plant DABB proteins and low sequence identity with the functionally distinct bacterial DABB proteins, the catalytic mechanism of OAC has remained unclear. To clarify the intimate catalytic mechanism of OAC, the enzyme was overexpressed in Escherichia coli and crystallized using the vapour-diffusion method. The crystals diffracted X-rays to 1.40 Å resolution and belonged to space group P3121 or P3221, with unit-cell parameters a = b = 47.3, c = 176.0 Å. Further crystallographic analysis will provide valuable insights into the structure-function relationship and catalytic mechanism of OAC.

Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads.

PubMed

Russo, Ethan B; Marcu, Jahan

2017-01-01

The golden age of cannabis pharmacology began in the 1960s as Raphael Mechoulam and his colleagues in Israel isolated and synthesized cannabidiol, tetrahydrocannabinol, and other phytocannabinoids. Initially, THC garnered most research interest with sporadic attention to cannabidiol, which has only rekindled in the last 15 years through a demonstration of its remarkably versatile pharmacology and synergy with THC. Gradually a cognizance of the potential of other phytocannabinoids has developed. Contemporaneous assessment of cannabis pharmacology must be even far more inclusive. Medical and recreational consumers alike have long believed in unique attributes of certain cannabis chemovars despite their similarity in cannabinoid profiles. This has focused additional research on the pharmacological contributions of mono- and sesquiterpenoids to the effects of cannabis flower preparations. Investigation reveals these aromatic compounds to contribute modulatory and therapeutic roles in the cannabis entourage far beyond expectations considering their modest concentrations in the plant. Synergistic relationships of the terpenoids to cannabinoids will be highlighted and include many complementary roles to boost therapeutic efficacy in treatment of pain, psychiatric disorders, cancer, and numerous other areas. Additional parts of the cannabis plant provide a wide and distinct variety of other compounds of pharmacological interest, including the triterpenoid friedelin from the roots, canniprene from the fan leaves, cannabisin from seed coats, and cannflavin A from seed sprouts. This chapter will explore the unique attributes of these agents and demonstrate how cannabis may yet fulfil its potential as Mechoulam's professed "pharmacological treasure trove." © 2017 Elsevier Inc. All rights reserved.

Hair analysis for Δ(9) -tetrahydrocannabinolic acid A (THCA-A) and Δ(9) -tetrahydrocannabinol (THC) after handling cannabis plant material.

PubMed

Moosmann, Bjoern; Roth, Nadine; Auwärter, Volker

2016-01-01

A previous study has shown that Δ(9) -tetrahydrocannabinolic acid A (THCA-A), the non-psychoactive precursor of Δ(9) -tetrahydrocannabinol (THC) in the cannabis plant does not get incorporated in relevant amounts into the hair through the bloodstream after repeated oral intake. However, THCA-A can be measured in forensic hair samples in concentrations often exceeding the detected THC concentrations. To investigate whether the handling of cannabis plant material prior to consumption is a contributing factor for THC-positive hair results and also the source for THCA-A findings in hair, a study comprising ten participants was conducted. In this study, the participants rolled a marijuana joint on five consecutive days and hair samples of each participant were obtained. Urine samples were taken to exclude cannabis consumption prior to and during the study. THCA-A and THC could be detected in the hair samples from all participants taken at the end of the exposure period (concentration range: 15-1800 pg/mg for THCA-A and < 10-93 pg/mg for THC). Four weeks after the first exposure, THCA-A could still be detected in the hair samples of nine participants (concentration range: 4-57 pg/mg). Furthermore, THC could be detected in the hair samples of five participants (concentration range: < 10-17 pg/mg). Based on these results, it can be concluded that at least parts of the THC as well as the major part of THCA-A found in routine hair analysis derives from external contamination caused by direct transfer through contaminated fingers. This finding is of particular interest in interpreting THC-positive hair results of children or partners of cannabis users, where such a transfer can occur due to close body contact. Analytical findings may be wrongly interpreted as a proof of consumption or at least passive exposure to cannabis smoke. Such misinterpretation could lead to severe consequences for the people concerned. Copyright © 2015 John Wiley & Sons, Ltd.

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.

[Ttextual research of Cannabis sativa varieties and medicinal part].

PubMed

Wei, Yingfang; Wang, Huadong; Guo, Shanshan; Yan, Jie; Long, Fei

2010-07-01

To determine the medicinal part and varieties of Cannabis Sativa through herbal textual research to Provide bibliographic reference for clinical application. Herbal textual research of C. Sativa from ancient herbal works and modern data analysis. Through the herbal textual research, the plant of the C. sativa, for Fructus Cannabis used now is identical with that described in ancient herbal literatures. People did not make a sharp distinction on medicinal part of C. sativa in the early stage literatures, female inflorescence and unripe fruit, fruit and kernel of seed were all used. Since Taohongjing realized the toxicity ofpericarp, all the herbal and prescription works indicate that the pericarp shall be removed before usage and only the kernel can be used. However, in modem literatures, both fruit and kernel can be used as medicinal part. The plants for Fructus Cannabis described in modern and ancient literatures are identical. The base of the original plant is the same either in ancient or modern. And the toxicity of the fruit is more than that of the kernel. The kernel is the exact medicinal part of C. Sativa.

Cannabis clubs in Uruguay: The challenges of regulation.

PubMed

Queirolo, Rosario; Boidi, Maria Fernanda; Cruz, José Miguel

2016-08-01

The Uruguayan Cannabis Clubs (UCCs) constitute one of three ways to obtain cannabis under the new cannabis regulation laws. These organizations, formed by up to 45 adults and with a legal limit to grow up to 99 plants, appear to provide a safe method of procuring cannabis in a country that is trying to regulate aspects of cannabis production and distribution. This article describes the operations of the UCCs and the challenges these organizations face. The paper draws on data from in-depth interviews conducted with representatives of UCCs and conversations with government officials conducted between March and August of 2015. We collected information about membership, facilities and forms of organization, methods of cannabis cultivation and distribution, and activities within the community. This article describes how UCCs are formed, their resources, rules for cannabis production and distribution; and their relationships with government institutions and the community. Data show that UCCs face four main challenges: compliance with the extant regulation, financial sustainability, tolerance from the community, and collective action dilemmas. Organizational challenges are as frequent in Uruguay as in other country where cannabis clubs exist, however this paper shows that in order to be sustainable, UCCs need to address issues of collective action, financial sustainability, and possible competition with cannabis distribution via pharmacies that could diminish membership. In the case of Uruguay, UCCs are part of a regulation effort, though they may not be preferred over other legal alternatives already in place. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification of Cannabis sativa L. using the 1-kbTHCA synthase-fluorescence in situ hybridization probe.

PubMed

Jeangkhwoa, Pattraporn; Bandhaya, Achirapa; Umpunjun, Puangpaka; Chuenboonngarm, Ngarmnij; Panvisavas, Nathinee

2017-03-01

This study reports a successful application of fluorescence in situ hybridization (FISH) technique in the identification of Cannabis sativa L. cells recovered from fresh and dried powdered plant materials. Two biotin-16-dUTP-labeled FISH probes were designed from the Cannabis-specific tetrahydrocannabinolic acid synthase (THCAS) gene and the ITS region of the 45S rRNA gene. Specificity of probe-target hybridization was tested against the target and 4 non-target plant species, i.e., Humulus lupulus, Mitragyna speciosa, Papaver sp., and Nicotiana tabacum. The 1-kb THCA synthase hybridization probe gave Cannabis-specific hybridization signals, unlike the 700-bp Cannabis-ITS hybridization probe. Probe-target hybridization was also confirmed against 20 individual Cannabis plant samples. The 1-kb THCA synthase and 700-bp Cannabis-ITS hybridization probes clearly showed 2 hybridization signals per cell with reproducibility. The 1-kb THCA synthase probe did not give any FISH signal when tested against H. lupulus, its closely related member of the Canabaceae family. It was also showed that 1-kb THCA synthase FISH probe can be applied to identify small amount of dried powdered Cannabis material with an addition of rehydration step prior to the experimental process. This study provided an alternative identification method for Cannabis trace. Copyright © 2016. Published by Elsevier B.V.

Cannabis for inflammatory bowel disease.

PubMed

Naftali, Timna; Mechulam, Raphael; Lev, Lihi Bar; Konikoff, Fred M

2014-01-01

The marijuana plant Cannabis sativa has been used for centuries as a treatment for a variety of ailments. It contains over 60 different cannabinoid compounds. Studies have revealed that the endocannabinoid system is involved in almost all major immune events. Cannabinoids may, therefore, be beneficial in inflammatory disorders. In murine colitis, cannabinoids decrease histologic and microscopic inflammation. In humans, cannabis has been used to treat a plethora of gastrointestinal problems, including anorexia, emesis, abdominal pain, diarrhea, and diabetic gastroparesis. Despite anecdotal reports on medical cannabis in inflammatory bowel disease (IBD), there are few controlled studies. In an observational study in 30 patients with Crohn's disease (CD), we found that medical cannabis was associated with improvement in disease activity and reduction in the use of other medications. In a more recent placebo-controlled study in 21 chronic CD patients, we showed a decrease in the CD activity index >100 in 10 of 11 subjects on cannabis compared to 4 of 10 on placebo. Complete remission was achieved in 5 of 11 subjects in the cannabis group and 1 of 10 in the placebo group. Yet, in an additional study, low-dose cannabidiol did not have an effect on CD activity. In summary, evidence is gathering that manipulating the endocannabinoid system can have beneficial effects in IBD, but further research is required to declare cannabinoids a medicine. We need to establish the specific cannabinoids, as well as appropriate medical conditions, optimal dose, and mode of administration, to maximize the beneficial effects while avoiding any potential harmful effects of cannabinoid use. © 2014 S. Karger AG, Basel.

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.

Filling in the blanks. An estimation of illicit cannabis growers' profits in Belgium.

PubMed

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

2014-05-01

As a result of increased pressure on cannabis cultivation in The Netherlands, the number of confiscated indoor cannabis plantations in Belgium is rising. Although increases are reported for all plantations sizes, half of the seized plantations contain less than 50 plants. In this study, factors and variables that influence costs and benefits of indoor cannabis cultivation are investigated as well as how these costs and benefits vary between different cannabis grower types. Real-situation data of four growers were used to perform financial analyses. Costs included fixed and variable material costs, as well as opportunity costs. Gross revenue per grow cycle was calculated based on most recent forensic findings for illicit Belgian cannabis plantations and was adjusted for the risk of getting caught. Finally, gross revenues and return on costs (ROC) were calculated over 1 year (4 cycles). Financial analysis shows that in all cases gross revenues as well as ROC are considerable, even after a single growth cycle. Highest profitability was found for large-scale (600 plants, ROC=6.8) and mid-scale plantations (150 plants, ROC=6.0). However, industrial plantations (23,000 plants, ROC=1.4) and micro-scale plantations (5 plants, ROC=2.8) are also highly remunerative. Shift of police focus away from micro-scale growers, least likely to be involved in criminal gangs, to large-scale and industrial scale plantations would influence costs as a result of changing risks of getting caught. However, sensitivity analysis shows that this does not significantly influence the conclusions on profitability of different types of indoor cannabis growers. Seizure and confiscation of profits are important elements in the integral and integrated policy approach required for tackling illicit indoor cannabis plantations. The large return of costs evidenced in the present study, underpin the policy relevance of confiscating those illicit profits as part of enforcement. Copyright © 2014 Elsevier B

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

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.

Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol.

PubMed

Romano, Barbara; Borrelli, Francesca; Pagano, Ester; Cascio, Maria Grazia; Pertwee, Roger G; Izzo, Angelo A

2014-04-15

Colon cancer is a major public health problem. Cannabis-based medicines are useful adjunctive treatments in cancer patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS, i.e. CBD botanical drug substance, on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo. Proliferation was evaluated in colorectal carcinoma (DLD-1 and HCT116) as well as in healthy colonic cells using the MTT assay. CBD BDS binding was evaluated by its ability to displace [(3)H]CP55940 from human cannabinoid CB1 and CB2 receptors. In vivo, the effect of CBD BDS was examined on the preneoplastic lesions (aberrant crypt foci), polyps and tumours induced by the carcinogenic agent azoxymethane (AOM) as well as in a xenograft model of colon cancer in mice. CBD BDS and CBD reduced cell proliferation in tumoral, but not in healthy, cells. The effect of CBD BDS was counteracted by selective CB1 and CB2 receptor antagonists. Pure CBD reduced cell proliferation in a CB1-sensitive antagonist manner only. In binding assays, CBD BDS showed greater affinity than pure CBD for both CB1 and CB2 receptors, with pure CBD having very little affinity. In vivo, CBD BDS reduced AOM-induced preneoplastic lesions and polyps as well as tumour growth in the xenograft model of colon cancer. CBD BDS attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabis-based medicines in cancer patients. Copyright © 2013 Elsevier GmbH. All rights reserved.

Plant extracts: sense or nonsense?

PubMed

Madersbacher, Stephan; Berger, Ingrid; Ponholzer, Anton; Marszalek, Martin

2008-01-01

To assess the current role of plant extracts in the medical management of lower urinary tract symptoms due to benign prostatic enlargement/benign prostatic obstruction. In 2006, two clinical trials meeting the WHO benign prostatic hyperplasia consensus conference criteria (randomized against placebo/standard therapy, study duration 12 months) were published. One trial compared a saw palmetto extract with placebo. This industry-independent trial published in the New England Journal of Medicine was negative, that is, this saw palmetto extract had no effect on symptoms, Qmax and postvoid residual volume. In another trial, a saw palmetto/urtica combination was compared with tamsulosin. After 12 months, the improvement of symptoms was identical in both study arms. No detailed data were presented, however, on Qmax, postvoid residual or prostate volume. The biological mechanisms of plant extracts in vivo are still unknown and the numerous metaanalyses cannot supplement high-quality prospective trials. Further prospective studies according to WHO benign prostatic hyperplasia standards are required to reliably determine the role of plant extracts in contemporary lower urinary tract symptoms management and to be able to answer the question in the title: 'plant extracts: sense or nonsense?' Plant extracts are currently not recommended by the American and European Association of Urology benign prostatic hyperplasia guidelines.

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.

Larval susceptibility of Aloe barbadensis and Cannabis sativa against Culex quinquefasciatus, the filariasis vector.

PubMed

Maurya, Prejwltta; Mohan, Lalit; Sharma, Preeti; Srivastava, C N

2008-11-01

Larvicidal potential of petroleum ether, carbon tetrachloride and methanol extracts of Aloe barbadensis and Cannabis sativa has been investigated against Culex quinquefasciatus. Among the extracts examined, Carbon tetrachloride extract (Cte) of Aloe barbadensis was the most effective with LC50 values of 15.31 and 11.01 ppm after 24 and 48 hr of exposure, respectively followed by pertoleum ether extract (Pee) of A barbadensis, Cte of C. sativa, methanol extract (Mee) of A. barbadensis, methanol and petroleum ether of C. saliva, LC, being 25.97, 88.51, 144.44, 160.78 and 294.42 ppm affer 24hr and 16.60, 68.69, 108.38, 71.71 and 73.32 ppm after 48 hr of post treatment, respectively. Cte of both the plants exhibits potential larvicidal activity and can be used as ecofriendly alternative in the management of the filariasis vector, Culex quinquefasciatus.

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.

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

The Evolution of Veteran Affairs Healthcare - Is It High Time for Cannabis Treatment

DTIC Science & Technology

2015-10-01

be considering recommending medicinal cannabis to a patient Reprint from The Open Neurology Journal, “ Medical Marijuana: Clearing Away the Smoke...the plant.9 Veterans in Support of Medical Marijuana are lobbying for more states to legalize cannabis for medical use. However, their primary...recommending cannabis for various illnesses and discomforts. More than 100 papers were published in the Western medical literature on the medical uses of

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

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.

a Hyperspectral Based Method to Detect Cannabis Plantation in Inaccessible Areas

NASA Astrophysics Data System (ADS)

Houmi, M.; Mohamadi, B.; Balz, T.

2018-04-01

The increase in drug use worldwide has led to sophisticated illegal planting methods. Most countries depend on helicopters, and local knowledge to identify such illegal plantations. However, remote sensing techniques can provide special advantages for monitoring the extent of illegal drug production. This paper sought to assess the ability of the Satellite remote sensing to detect Cannabis plantations. This was achieved in two stages: 1- Preprocessing of Hyperspectral data EO-1, and testing the capability to collect the spectral signature of Cannabis in different sites of the study area (Morocco) from well-known Cannabis plantation fields. 2- Applying the method of Spectral Angle Mapper (SAM) based on a specific angle threshold on Hyperion data EO-1 in well-known Cannabis plantation sites, and other sites with negative Cannabis plantation in another study area (Algeria), to avoid any false Cannabis detection using these spectra. This study emphasizes the benefits of using hyperspectral remote sensing data as an effective detection tool for illegal Cannabis plantation in inaccessible areas based on SAM classification method with a maximum angle (radians) less than 0.03.

Cannabis finds its way into treatment of Crohn's disease.

PubMed

Schicho, Rudolf; Storr, Martin

2014-01-01

In ancient medicine, cannabis has been widely used to cure disturbances and inflammation of the bowel. A recent clinical study now shows that the medicinal plant Cannabis sativa has lived up to expectations and proved to be highly efficient in cases of inflammatory bowel diseases. In a prospective placebo-controlled study, it has been shown what has been largely anticipated from anecdotal reports, i.e. that cannabis produces significant clinical benefits in patients with Crohn's disease. The mechanisms involved are not yet clear but most likely include peripheral actions on cannabinoid receptors 1 and 2, and may also include central actions. © 2013 S. Karger AG, Basel.

Risks associated with the non-medicinal use of cannabis.

PubMed

Hoch, Eva; Bonnetn, Udo; Thomasius, Rainer; Ganzer, Florian; Havemann-Reinecke, Ursula; Preuss, Ulrich W

2015-04-17

Cannabis is the most commonly consumed illicit drug around the world; in Germany, about 4.5% of all adults use it each year. Intense cannabis use is associated with health risks. Evidence-based treatments are available for health problems caused by cannabis use. Selective literature review based on a search of the PubMed database, with special emphasis on systematic reviews, meta-analyses, cohort studies, randomized controlled trials (RCTs), case-control studies, and treatment guidelines. The delta-9-tetrahydrocannabinol content of cannabis products is rising around the world as a result of plant breeding, while cannabidiol, in contrast, is often no longer detectable. Various medical conditions can arise acutely after cannabis use, depending on the user's age, dose, frequency, mode and situation of use, and individual disposition; these include panic attacks, psychotic symptoms, deficient attention, impaired concentration, motor incoordination, and nausea. In particular, intense use of high doses of cannabis over many years, and the initiation of cannabis use in adolescence, can be associated with substance dependence (DSM-5; ICD-10), specific withdrawal symptoms, cognitive impairment, affective disorders, psychosis, anxiety disorders, and physical disease outside the brain (mainly respiratory and cardiovascular conditions). At present, the most effective way to treat cannabis dependence involves a combination of motivational encouragement, cognitive behavioral therapy, and contingency management (level 1a evidence). For adolescents, family therapy is also recommended (level 1a evidence). No pharmacological treatments can be recommended to date, as evidence for their efficacy is lacking. Further research is needed to elucidate the causal relationships between intense cannabis use and potential damage to physical and mental health. Health problems due to cannabis use can be effectively treated.

Cannabis and Anti-Cancer Drugs: Societal Usage and Expected Pharmacological Interactions - A Review.

PubMed

Bouquié, Régis; Deslandes, Guillaume; Mazaré, Hélène; Cogné, Marion; Mahé, Julien; Grégoire, Matthieu; Jolliet, Pascale

2018-04-16

Cannabis is a plant that has been used for centuries to relieve a wide range of symptoms. Since the 1960s, interest in medical research into this plant has grown steadily. Already very popular for recreational use, a growing number of consumers not accustomed to using cannabis for psychoactive purposes, have begun to use it as an alternative or complement to mainstream pharmaceutical medicines. The principal unsubstantiated or "social" uses of cannabis are based mainly on data that is at best controversial, but usually not scientifically proven. The aim of this review is to identify the scientific basis and reasons that lead patients with cancer to consume cannabis, and also to identify whether there is a risk of interaction between cannabis and anti-cancer medicines through drug transporters (P-glycoprotein and other ABC-superfamily members) Cytochromes P450 (3A, 1A, 2B, 2C 2D families…) and glucuronyl-transferases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cannabis: A Neurological Remedy or a Drug of Abuse in India.

PubMed

Biswas, Pronit; Mishra, Pooja; Bose, Devasish; Durgbanshi, Abhilasha

2017-01-01

Since ancient times, the use of cannabis as a medicine is well documented due to its potential therapeutic activity while subsequently its use as drug of abuse spread increasingly. The present review sought to give an insight in the history of medical and recreational use of cannabis in India. Indian use of cannabis dates back to Vedic time, mostly for the ritualistic and religious purposes, as documented in the ancient literature. It was India that introduced the medical use of cannabis to neighboring countries. Nevertheless, in the same India, medical use did not propagate due to religious and social stigma related to the plant itself. The pharmacoactive constituents of cannabis and their therapeutic values in Ayurvetic medicine have been here described together with the adverse effects they can cause with special reference to neurological ones, including withdrawal symptoms. Finally, how cannabis made its route to the Indian society has also been discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cannabis: a controversial 21st-century drug of antiquity.

PubMed

Greydanus, D; Holt, M

2014-05-01

Cannabis consumption has been popular for thousands of years and its historical use is noted in many parts of the world including ancient China, India, the Middle East. It is currently the most popular illicit drug in the world, is being utilized as a medicinal plant, and many parts of the world are legalizing this drug. This discussion considers various aspects of cannabis use including its prevalence, history, co-morbid drug abuse, designer cannabinoids, psychiatric adverse effects, medical adverse effects, and management options. The youth of the world should be comprehensively taught that cannabis is neither a safe nor a benign drug. Prevention with comprehensive drug education is the best plan for our youth since management of a chronic or heavy cannabis consummer remains difficult and fraught with failure if cessation is the goal. Caveat emptor!

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.

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

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

Nabilone therapy for cannabis withdrawal presenting as protracted nausea and vomiting.

PubMed

Lam, Philip W; Frost, David W

2014-09-22

Cannabis is one of the most commonly used recreational drugs worldwide. Psychoactive properties of the principal compound, δ-9-tetrahydrocannabinol include euphoria, a sense of relaxation and increased appetite. Chronic cannabis use has been associated with the development of a withdrawal syndrome on abrupt discontinuation. Withdrawal symptoms typically begin within 24 h of abstinence and manifest as irritability, nervousness, sleep disturbances and decreased appetite. There is growing evidence that supports the use of plant-derived and synthetic cannabinoids for the treatment of cannabis withdrawal. In this case report, we present 20-year-old woman who developed protracted nausea and vomiting secondary to cannabis withdrawal and was successfully treated with nabilone. Nausea and vomiting is not listed in the Diagnostic and Statistical Manual-5 diagnostic criteria for cannabis withdrawal syndrome and is an uncommon symptom presentation. 2014 BMJ Publishing Group Ltd.

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.

Why is it so difficult to determine the yield of indoor cannabis plantations? A case study from the Netherlands.

PubMed

Vanhove, Wouter; Maalsté, Nicole; Van Damme, Patrick

2017-07-01

Together, the Netherlands and Belgium are the largest indoor cannabis producing countries in Europe. In both countries, legal prosecution procedure of convicted illicit cannabis growers usually includes recovery of the profits gained. However, it is not easy to make a reliable estimation of the latter profits, due to the wide range of factors that determine indoor cannabis yields and eventual selling prices. In the Netherlands, since 2005, a reference model is used that assumes a constant yield (g) per plant for a given indoor cannabis plant density. Later, in 2011, a new model was developed in Belgium for yield estimation of Belgian indoor cannabis plantations that assumes a constant yield per m 2 of growth surface, provided that a number of growth conditions are met. Indoor cannabis plantations in the Netherlands and Belgium share similar technical characteristics. As a result, for indoor cannabis plantations in both countries, both aforementioned yield estimation models should yield similar yield estimations. By means of a real-case study from the Netherlands, we show that the reliability of both models is hampered by a number of flaws and unmet preconditions. The Dutch model is based on a regression equation that makes use of ill-defined plant development stages, assumes a linear plant growth, does not discriminate between different plantation size categories and does not include other important yield determining factors (such as fertilization). The Belgian model addresses some of the latter shortcomings, but its applicability is constrained by a number of pre-conditions including plantation size between 50 and 1000 plants; cultivation in individual pots with peat soil; 600W (electrical power) assimilation lamps; constant temperature between 20°C and 30°C; adequate fertilizer application and plants unaffected by pests and diseases. Judiciary in both the Netherlands and Belgium require robust indoor cannabis yield models for adequate legal prosecution of

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.

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

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

Broad-Scale Genetic Diversity of Cannabis for Forensic Applications.

PubMed

Dufresnes, Christophe; Jan, Catherine; Bienert, Friederike; Goudet, Jérôme; Fumagalli, Luca

2017-01-01

Cannabis (hemp and marijuana) is an iconic yet controversial crop. On the one hand, it represents a growing market for pharmaceutical and agricultural sectors. On the other hand, plants synthesizing the psychoactive THC produce the most widespread illicit drug in the world. Yet, the difficulty to reliably distinguish between Cannabis varieties based on morphological or biochemical criteria impedes the development of promising industrial programs and hinders the fight against narcotrafficking. Genetics offers an appropriate alternative to characterize drug vs. non-drug Cannabis. However, forensic applications require rapid and affordable genotyping of informative and reliable molecular markers for which a broad-scale reference database, representing both intra- and inter-variety variation, is available. Here we provide such a resource for Cannabis, by genotyping 13 microsatellite loci (STRs) in 1 324 samples selected specifically for fibre (24 hemp varieties) and drug (15 marijuana varieties) production. We showed that these loci are sufficient to capture most of the genome-wide diversity patterns recently revealed by NGS data. We recovered strong genetic structure between marijuana and hemp and demonstrated that anonymous samples can be confidently assigned to either plant types. Fibres appear genetically homogeneous whereas drugs show low (often clonal) diversity within varieties, but very high genetic differentiation between them, likely resulting from breeding practices. Based on an additional test dataset including samples from 41 local police seizures, we showed that the genetic signature of marijuana cultivars could be used to trace crime scene evidence. To date, our study provides the most comprehensive genetic resource for Cannabis forensics worldwide.

Broad-Scale Genetic Diversity of Cannabis for Forensic Applications

PubMed Central

Dufresnes, Christophe; Jan, Catherine; Bienert, Friederike; Goudet, Jérôme; Fumagalli, Luca

2017-01-01

Cannabis (hemp and marijuana) is an iconic yet controversial crop. On the one hand, it represents a growing market for pharmaceutical and agricultural sectors. On the other hand, plants synthesizing the psychoactive THC produce the most widespread illicit drug in the world. Yet, the difficulty to reliably distinguish between Cannabis varieties based on morphological or biochemical criteria impedes the development of promising industrial programs and hinders the fight against narcotrafficking. Genetics offers an appropriate alternative to characterize drug vs. non-drug Cannabis. However, forensic applications require rapid and affordable genotyping of informative and reliable molecular markers for which a broad-scale reference database, representing both intra- and inter-variety variation, is available. Here we provide such a resource for Cannabis, by genotyping 13 microsatellite loci (STRs) in 1 324 samples selected specifically for fibre (24 hemp varieties) and drug (15 marijuana varieties) production. We showed that these loci are sufficient to capture most of the genome-wide diversity patterns recently revealed by NGS data. We recovered strong genetic structure between marijuana and hemp and demonstrated that anonymous samples can be confidently assigned to either plant types. Fibres appear genetically homogeneous whereas drugs show low (often clonal) diversity within varieties, but very high genetic differentiation between them, likely resulting from breeding practices. Based on an additional test dataset including samples from 41 local police seizures, we showed that the genetic signature of marijuana cultivars could be used to trace crime scene evidence. To date, our study provides the most comprehensive genetic resource for Cannabis forensics worldwide. PMID:28107530

[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.

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.

Monitoring Metabolite Profiles of Cannabis sativa L. Trichomes during Flowering Period Using 1H NMR-Based Metabolomics and Real-Time PCR.

PubMed

Happyana, Nizar; Kayser, Oliver

2016-08-01

Cannabis sativa trichomes are glandular structures predominantly responsible for the biosynthesis of cannabinoids, the biologically active compounds unique to this plant. To the best of our knowledge, most metabolomic works on C. sativa that have been reported previously focused their investigations on the flowers and leaves of this plant. In this study, (1)H NMR-based metabolomics and real-time PCR analysis were applied for monitoring the metabolite profiles of C. sativa trichomes, variety Bediol, during the last 4 weeks of the flowering period. Partial least squares discriminant analysis models successfully classified metabolites of the trichomes based on the harvest time. Δ (9)-Tetrahydrocannabinolic acid (1) and cannabidiolic acid (2) constituted the vital differential components of the organic preparations, while asparagine, glutamine, fructose, and glucose proved to be their water-extracted counterparts. According to RT-PCR analysis, gene expression levels of olivetol synthase and olivetolic acid cyclase influenced the accumulation of cannabinoids in the Cannabis trichomes during the monitoring time. Moreover, quantitative (1)H NMR and RT-PCR analysis of the Cannabis trichomes suggested that the gene regulation of cannabinoid biosynthesis in the C. sativa variety Bediol is unique when compared with other C. sativa varieties. Georg Thieme Verlag KG Stuttgart · New York.

Mapping regulatory models for medicinal cannabis: a matrix of options.

PubMed

Belackova, Vendula; Shanahan, Marian; Ritter, Alison

2017-05-30

Objective The aim of the present study was to develop a framework for assessing regulatory options for medicinal cannabis in Australia. Methods International regulatory regimes for medicinal cannabis were reviewed with a qualitative policy analysis approach and key policy features were synthesised, leading to a conceptual framework that facilitates decision making across multiple dimensions. Results Two central organising dimensions of medicinal cannabis regulation were identified: cannabis supply and patient authorisation (including patient access). A number of the different supply options can be matched with a number of different patient authorisation options, leading to a matrix of possible regulatory regimes. Conclusions The regulatory options, as used internationally, involve different forms of cannabis (synthetic and plant-based pharmaceutical preparations or herbal cannabis) and the varying extent to which patient authorisation policies and procedures are stringently or more loosely defined. The optimal combination of supply and patient authorisation options in any jurisdiction that chooses to make medicinal cannabis accessible will depend on policy goals. What is known about the topic? Internationally, regulation of medicinal cannabis has developed idiosyncratically, depending on formulations that were made available and local context. There has been no attempt to date in the scientific literature to systematically document the variety of regulatory possibilities for medicinal cannabis. What does this paper add? This paper presents a new conceptual schema for considering options for the regulation of medicinal cannabis, across both supply and patient authorisation aspects. What are the implications for practitioners? The design of regulatory systems in Australia, whether for pharmaceutical or herbal products, is a vital issue for policy makers right now as federal and state and territory governments grapple with the complexities of medicinal cannabis

Cannabis cultivation in Spain: A profile of plantations, growers and production systems.

PubMed

Alvarez, Arturo; Gamella, Juan F; Parra, Iván

2016-11-01

The European market for cannabis derivatives is being transformed. The cultivation of cannabis within the EU and the shift of demand from hashish to domestic marihuana are key aspects of this transformation. Spain, formerly central to the trade of Moroccan hashish, is becoming a marihuana-producing country. The emergence of "import-substitution" has been researched in other EU countries, but thus far the Spanish case remains undocumented. This paper is based on analysis of data of 748 cannabis plantations seized by Spanish police in 2013. The sample comprises reports of seizures identified through a survey of online news and police reports. "Event-analysis" methods were applied to these sources. The analysis offers a typology of plantations, a profile of participants and the different production systems, and a model of regional distribution. Half of the plantations were small (less than 42 plants) and half contained between 100 and 1000 plants, with an average size of 261 plants. About three-quarters of plants were cultivated indoors using stolen electricity. 86% of all plants seized were from large-scale plantations (more than 220 plants). Most plantations were located along the Mediterranean coast, where population and tourism are concentrated. Over three-quarters of those indicted by police were Spanish (85%). Among the foreign owners of big plantations, Dutch nationals predominated. The number of seized plants by province was directly associated with the number of grow shops (β=0.962, p<0.001). The rise of large-scale cannabis plantations in the Spanish Mediterranean coast is increasingly replacing import of Moroccan hashish. Indoor cultivation supported by grow shops, that provide the technology and know-how, seem to be the dominant form of organization in this emerging industry. Large-scale plantations may have met most of the demand for marihuana in 2013. Copyright © 2016 Elsevier B.V. All rights reserved.

Work place drug testing of police officers after THC exposure during large volume cannabis seizures.

PubMed

Doran, Gregory S; Deans, Ralph; De Filippis, Carlo; Kostakis, Chris; Howitt, Julia A

2017-06-01

Police officers responsible for the seizure and removal of illegally grown cannabis plants from indoor and outdoor growing operations face the prospect of THC exposure while performing their work duties. As a result, a study investigating the amount of THC on hands and uniforms of officers during raids on cannabis growing houses (CGHs) and forest cannabis plantations (FCPs) and in the air at these sites was conducted. Swabs of gloves/hands, chests, and heads/necks were collected and analysed for THC. Results of hand swabs indicated that officers removing plants from FCPs were exposed to THC concentrations up to 20 times those involved in raids at CGHs, which was mainly associated with the number and size of plants seized. Air samples collected inside cannabis houses showed no detectable THC. Air samples collected inside the cargo area of the storage trucks used during FCP raids indicated that THC can be volatilised when lush plants are compressed by other seized plants loaded on top of them in the truck over a period of several days, allowing composting of plants at the bottom of the load to commence. The elevated temperature and humidity inside the truck may assist the decarboxylation of THCA to THC, as well as increasing the rate of volatilisation of THC. More than 100 urine samples were collected from officers in raids on both CGHs and FCPs and all tested negative for THC. Removal of cannabis plants by officers often resulted in cuts, abrasions and ruptured blisters on exposed skin surfaces, particularly at FCPs. The results in this study suggest that even when small areas of damaged skin are directly exposed to THC by contact transfer, the likelihood of showing a positive THC urine test is low. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

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.

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, 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

Cannabis (Cannabis sativa or C. indica) agriculture and the environment: a systematic, spatially-explicit survey and potential impacts

NASA Astrophysics Data System (ADS)

Butsic, Van; Brenner, Jacob C.

2016-04-01

Cannabis agriculture is a multi-billion dollar industry in the United States that is changing rapidly with policy liberalization. Anecdotal observations fuel speculation about associated environmental impacts, and there is an urgent need for systematic empirical research. An example from Humboldt County California, a principal cannabis-producing region, involved digitizing 4428 grow sites in 60 watersheds with Google Earth imagery. Grows were clustered, suggesting disproportionate impacts in ecologically important locales. Sixty-eight percent of grows were >500 m from developed roads, suggesting risk of landscape fragmentation. Twenty-two percent were on steep slopes, suggesting risk of erosion, sedimentation, and landslides. Five percent were <100 m from threatened fish habitat, and the estimated 297 954 plants would consume an estimated 700 000 m3 of water, suggesting risk of stream impacts. The extent and magnitude of cannabis agriculture documented in our study demands that it be regulated and researched on par with conventional agriculture.

[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.

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%).

Near infrared spectroscopy combined with chemometrics for growth stage classification of cannabis cultivated in a greenhouse from seized seeds.

PubMed

Borille, Bruna Tassi; Marcelo, Marcelo Caetano Alexandre; Ortiz, Rafael Scorsatto; Mariotti, Kristiane de Cássia; Ferrão, Marco Flôres; Limberger, Renata Pereira

2017-02-15

Cannabis sativa L. (cannabis, Cannabaceae), popularly called marijuana, is one of the oldest plants known to man and it is the illicit drug most used worldwide. It also has been the subject of increasing discussions from the scientific and political points of view due to its medicinal properties. In recent years in Brazil, the form of cannabis drug trafficking has been changing and the Brazilian Federal Police has exponentially increased the number of seizures of cannabis seeds sent by the mail. This new form of trafficking encouraged the study of cannabis seeds seized germinated in a greenhouse through NIR spectroscopy combined with chemometrics. The plants were cultivated in a homemade greenhouse under controlled conditions. In three different growth periods (5.5weeks, 7.5weeks and 10weeks), they were harvested, dried, ground and directly analyzed. The iPCA was used to select the best NIR spectral range (4000-4375cm -1 ) in order to develop unsupervised and supervised methods. The PCA and HCA showed a good separation between the three groups of cannabis samples at different growth stages. The PLS-DA and SVM-DA classified the samples with good results in terms of sensitivity and specificity. The sensitivity and specificity for SVM-DA classification were equal to unity. This separation may be due to the correlation of cannabinoids and volatile compounds concentration during the growth of the cannabis plant. Therefore, the growth stage of cannabis can be predicted by NIR spectroscopy and chemometric tools in the early stages of indoor cannabis cultivation. Copyright © 2016 Elsevier B.V. All rights reserved.

Near infrared spectroscopy combined with chemometrics for growth stage classification of cannabis cultivated in a greenhouse from seized seeds

NASA Astrophysics Data System (ADS)

Borille, Bruna Tassi; Marcelo, Marcelo Caetano Alexandre; Ortiz, Rafael Scorsatto; Mariotti, Kristiane de Cássia; Ferrão, Marco Flôres; Limberger, Renata Pereira

2017-02-01

Cannabis sativa L. (cannabis, Cannabaceae), popularly called marijuana, is one of the oldest plants known to man and it is the illicit drug most used worldwide. It also has been the subject of increasing discussions from the scientific and political points of view due to its medicinal properties. In recent years in Brazil, the form of cannabis drug trafficking has been changing and the Brazilian Federal Police has exponentially increased the number of seizures of cannabis seeds sent by the mail. This new form of trafficking encouraged the study of cannabis seeds seized germinated in a greenhouse through NIR spectroscopy combined with chemometrics. The plants were cultivated in a homemade greenhouse under controlled conditions. In three different growth periods (5.5 weeks, 7.5 weeks and 10 weeks), they were harvested, dried, ground and directly analyzed. The iPCA was used to select the best NIR spectral range (4000-4375 cm- 1) in order to develop unsupervised and supervised methods. The PCA and HCA showed a good separation between the three groups of cannabis samples at different growth stages. The PLS-DA and SVM-DA classified the samples with good results in terms of sensitivity and specificity. The sensitivity and specificity for SVM-DA classification were equal to unity. This separation may be due to the correlation of cannabinoids and volatile compounds concentration during the growth of the cannabis plant. Therefore, the growth stage of cannabis can be predicted by NIR spectroscopy and chemometric tools in the early stages of indoor cannabis cultivation.

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.

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

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.

Active-oxygen scavenging activity of plant extracts.

PubMed

Masaki, H; Sakaki, S; Atsumi, T; Sakurai, H

1995-01-01

To find antioxidative compounds present in plants, 65 types of plant extract were tested using the neotetrazolium method for evidence of superoxide anion-scavenging effects and 7 plant extracts were selected for further investigation. The activity of active-oxygen scavengers such as superoxide anion radicals, hydroxyl radicals, singlet oxygens and lipid peroxides in the 7 plant extracts (Aeseclus hippocastanum L., Hamamelis virginiana L. Polygonum cuspidatum Sieb., Quercus robur L., Rosemarinous officinalis L., Salvia officinalis L. and Sanguisorba officinalis L.) was examined in detail by both ESR spin-trapping and malondialdehyde generation. Furthermore, the active-oxygen scavenging activity of these plant extracts was evaluated using a murine dermal fibroblast culture system. Both Aeseclus hippocastanum L. and Hamamelis virginia L. were found to have strong active-oxygen scavenging activity of and protective activity against cell damage induced by active oxygen. Both Aeseclus hippocastanum L. and Hamamelis virginiana L. are proposed as potent plant extracts with potential application as anti-aging or anti-wrinkle material for the skin.

Therapeutic potential of cannabis in pain medicine.

PubMed

Hosking, R D; Zajicek, J P

2008-07-01

Advances in cannabis research have paralleled developments in opioid pharmacology whereby a psychoactive plant extract has elucidated novel endogenous signalling systems with therapeutic significance. Cannabinoids (CBs) are chemical compounds derived from cannabis. The major psychotropic CB delta-9-tetrahydrocannabinol (Delta(9)-THC) was isolated in 1964 and the first CB receptor (CB(1)R) was cloned in 1990. CB signalling occurs via G-protein-coupled receptors distributed throughout the body. Endocannabinoids are derivatives of arachidonic acid that function in diverse physiological systems. Neuronal CB(1)Rs modulate synaptic transmission and mediate psychoactivity. Immune-cell CB(2) receptors (CB(2)R) may down-regulate neuroinflammation and influence cyclooxygenase-dependent pathways. Animal models demonstrate that CBRs play a fundamental role in peripheral, spinal, and supraspinal nociception and that CBs are effective analgesics. Clinical trials of CBs in multiple sclerosis have suggested a benefit in neuropathic pain. However, human studies of CB-mediated analgesia have been limited by study size, heterogeneous patient populations, and subjective outcome measures. Furthermore, CBs have variable pharmacokinetics and can manifest psychotropism. They are currently licensed as antiemetics in chemotherapy and can be prescribed on a named-patient basis for neuropathic pain. Future selective peripheral CB(1)R and CB(2)R agonists will minimize central psychoactivity and may synergize opioid anti-nociception. This review discusses the basic science and clinical aspects of CB pharmacology with a focus on pain medicine.

Plant crude extracts could be the solution: extracts showing in vivo antitumorigenic activity.

PubMed

Amara, A A; El-Masry, M H; Bogdady, H H

2008-04-01

Screening active compounds from plants lead to discover new medicinal drugs which have efficient protection and treatment roles against various diseases including cancer. In our study, extracts from different plants represent seeds of: Gossypium barbadense, Ricinus communis, Sesamum indicum, Nigella sativa, Vinca rosea and Melia azedarah; fruits of: Xanthium occidental; flowers of: Atriplex nummularia; barks of: Cinnamomum zeylanicum; latex of: Ficus carica and rhizomes of: Curcuma longa and Zingiber officinale were tested in vivo using three subsequent bioassays: the BST (Brine Shrimp Toxicity bioassay), AWD (Agar well diffusion antimicrobial bioassay) and AtPDT (Agrobacterium tumefaciens Potato Disc Tumor bioassay). AWD technique omitted any extracts have antimicrobial activities while BST omitted any extract did not has physiological activity and determined the various LC(50) of each plant extract. For the first time, using a range of concentrations in the AtPDT modified protocol allowed the detection of tumor promotion caused by extract represented by A. nummularia. Using cluster analysis leads to classifying the different plant extracts activities to six groups regarding to their toxicity, antitumor activities and both of them. The extracts from edible plants represent 50% of the first and the second group which have the highest antitumor activities represented in F. caraica (group 1) and C. longa (group 2) as well as the non-edible plant extracts of Gossypium barbadense and Ricinus communis. A comparison study between the edible and herbaceous plants different extracts for their antitumor activities was performed. We recommended using the modified protocols used in this study for investigating more plants and using crude plant extracts which have antitumor activities in cancer treatment. Edible plants, which show in vivo antitumor activities, are recommended as save sources for antitumor compounds.

In Vitro Propagation of Cannabis sativa L. and Evaluation of Regenerated Plants for Genetic Fidelity and Cannabinoids Content for Quality Assurance.

PubMed

Lata, Hemant; Chandra, Suman; Khan, Ikhlas A; ElSohly, Mahmoud A

2016-01-01

Cannabis sativa L. (Marijuana; Cannabaceae), one of the oldest medicinal plants in the world, has been used throughout history for fiber, food, as well as for its psychoactive properties. The dioecious and allogamous nature of C. sativa is the major constraint to maintain the consistency in chemical profile and overall efficacy if grown from seed. Therefore, the present optimized in vitro propagation protocol of the selected elite germplasm via direct organogenesis and quality assurance protocols using genetic and chemical profiling provide an ideal pathway for ensuring the efficacy of micropropagated Cannabis sativa germplasm. A high frequency shoot organogenesis of C. sativa was obtained from nodal segments in 0.5 μM thidiazuron medium and 95 % in vitro rhizogenesis is obtained on half-strength MS medium supplemented with 500 mg/L activated charcoal and 2.5 μM indole-3-butyric acid. Inter Simple Sequence Repeats (ISSR) and Gas Chromatography-Flame Ionization Detection (GC-FID) are successfully used to monitor the genetic stability in micropropagated plants up to 30 passages in culture and hardened in soil for 8 months.

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.

Medical use of cannabis. Cannabidiol: a new light for schizophrenia?

PubMed

Deiana, Serena

2013-01-01

The medical properties of cannabis have been known for many centuries; its first documented use dates back to 2800 BC when it was described for its hallucinogenic and pain-relieving properties. In the first half of the twentieth century, a number of pharmaceutical companies marked cannabis for indications such as asthma and pain, but since then its use has sharply declined, mainly due to its unpredictable effects, but also for socio-political issues. Recently, great attention has been directed to the medical properties of phytocannabinoids present in the cannabis plant alongside the main constituent Δ⁹-Tetrahydrocannabinol (THC); these include cannabinoids such as cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabivarin (THCV). Evidence suggests an association between cannabis and schizophrenia: schizophrenics show a higher use of marijuana as compared to the healthy population. Additionally, the use of marijuana can trigger psychotic episodes in schizophrenic patients, and this has been ascribed to THC. Given the need to reduce the side effects of marketed antipsychotics, and their weak efficacy on some schizophrenic symptoms, cannabinoids have been suggested as a possible alternative treatment for schizophrenia. CBD, a non-psychoactive constituent of the Cannabis sativa plant, has been receiving growing attention for its anti-psychotic-like properties. Evidence suggests that CBD can ameliorate positive and negative symptoms of schizophrenia. Behavioural and neurochemical models suggest that CBD has a pharmacological profile similar to that of atypical anti-psychotic drugs and a clinical trial reported that this cannabinoid is a well-tolerated alternative treatment for schizophrenia. Copyright © 2012 John Wiley & Sons, Ltd.

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

Medical use of cannabis products: Lessons to be learned from Israel and Canada.

PubMed

Ablin, J; Ste-Marie, P A; Schäfer, M; Häuser, W; Fitzcharles, M-A

2016-02-01

The German government intends to reduce the barriers for the medical use of cannabis products. A discussion on the indications and contraindications of the medical use of cannabis and on the changes of the regulatory framework has already begun in Germany. It is useful to draw from the experiences of other countries with a more liberal medical use of cannabis. The Israeli and Canadian experience is outlined by physicians who have been charged with expertise on the medical use of cannabis by their jurisdiction. In Israel, only the plant-based cannabinoid nabiximol (mixture of tetrahydrocannabinol/cannabidiol) can be prescribed for spasticity/chronic pain in multiple sclerosis and for cancer pain. The costs of nabiximole are reimbursed by some, but not by all health maintenance organizations. The medical use of marijuana is permitted; however, it is strictly regulated by the government. Selected companies are allowed to produce marijuana for medical use, and only certain physicians are licensed to prescribe marijuana as a therapeutic drug for specific indications such as chronic neuropathic, and cancer pain, inflammatory bowel diseases, or posttraumatic stress disorder if conventional treatments have failed. The costs of marijuana are not reimbursed by health insurance companies. In Canada, synthetic cannabinoids and the plant-based (nabiximol) are licensed for neuropathic and cancer pain, HIV-related anorexia and chemotherapy-associate nausea. The costs of these synthetic cannabinoids are covered by health insurance companies. The medical use of marijuana as a treatment option is allowed for individual patients suffering from any medical condition when authorized by a medical practitioner or nurse. Licensed producers are the only source for patients to newly access medical cannabis, although those with previous permission to grow may continue cultivation at the present time. The costs of marijuana are not reimbursed by health insurance companies. There are multiple

Assessment of cannabinoids content in micropropagated plants of Cannabis sativa and their comparison with conventionally propagated plants and mother plant during developmental stages of growth.

PubMed

Chandra, Suman; Lata, Hemant; Mehmedic, Zlatko; Khan, Ikhlas A; ElSohly, Mahmoud A

2010-05-01

Gas chromatography-flame ionization detection (GC-FID) was used to assess the chemical profile and quantification of cannabinoids to identify the differences, if existing, in the chemical constituents of in vitro propagated plants (IVP), conventionally grown plants (VP) and indoor grown mother plants (MP-Indoor) of a high THC yielding variety of Cannabis sativa L. during different developmental stages of growth. In general, THC content in all groups increased with plant age up to a highest level during the budding stage where the THC content reached a plateau before the onset of senescence. The pattern of changes observed in the concentration of other cannabinoids content with plants age has followed a similar trend in all groups of plants. Qualitatively, cannabinoids profiles obtained using GC-FID, in MP-indoor, VP and IVP plants were found to be similar to each other and to that of the field grown mother plant (MP field) of C. sativa. Minor differences observed in cannabinoids concentration within and among the groups were not found to be statistically significant. Our results confirm the clonal fidelity of IVP plants of C. sativa and suggest that the biochemical mechanism used in this study to produce the micropropagated plants does not affect the metabolic content and can be used for the mass propagation of true to type plants of this species for commercial pharmaceutical use. Georg Thieme Verlag KG Stuttgart. New York.

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.

The draft genome and transcriptome of Cannabis sativa.

PubMed

van Bakel, Harm; Stout, Jake M; Cote, Atina G; Tallon, Carling M; Sharpe, Andrew G; Hughes, Timothy R; Page, Jonathan E

2011-10-20

Cannabis sativa has been cultivated throughout human history as a source of fiber, oil and food, and for its medicinal and intoxicating properties. Selective breeding has produced cannabis plants for specific uses, including high-potency marijuana strains and hemp cultivars for fiber and seed production. The molecular biology underlying cannabinoid biosynthesis and other traits of interest is largely unexplored. We sequenced genomic DNA and RNA from the marijuana strain Purple Kush using shortread approaches. We report a draft haploid genome sequence of 534 Mb and a transcriptome of 30,000 genes. Comparison of the transcriptome of Purple Kush with that of the hemp cultivar 'Finola' revealed that many genes encoding proteins involved in cannabinoid and precursor pathways are more highly expressed in Purple Kush than in 'Finola'. The exclusive occurrence of Δ9-tetrahydrocannabinolic acid synthase in the Purple Kush transcriptome, and its replacement by cannabidiolic acid synthase in 'Finola', may explain why the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) is produced in marijuana but not in hemp. Resequencing the hemp cultivars 'Finola' and 'USO-31' showed little difference in gene copy numbers of cannabinoid pathway enzymes. However, single nucleotide variant analysis uncovered a relatively high level of variation among four cannabis types, and supported a separation of marijuana and hemp. The availability of the Cannabis sativa genome enables the study of a multifunctional plant that occupies a unique role in human culture. Its availability will aid the development of therapeutic marijuana strains with tailored cannabinoid profiles and provide a basis for the breeding of hemp with improved agronomic characteristics.

Evaluating the public health impacts of legalizing recreational cannabis use in the United States.

PubMed

Hall, Wayne; Lynskey, Michael

2016-10-01

Since 2012 four US states have legalized the retail sale of cannabis for recreational use by adults, and more are likely to follow. This report aimed to (1) briefly describe the regulatory regimes so far implemented; (2) outline their plausible effects on cannabis use and cannabis-related harm; and (3) suggest what research is needed to evaluate the public health impact of these policy changes. We reviewed the drug policy literature to identify: (1) plausible effects of legalizing adult recreational use on cannabis price and availability; (2) factors that may increase or limit these effects; (3) pointers from studies of the effects of legalizing medical cannabis use; and (4) indicators of cannabis use and cannabis-related harm that can be monitored to assess the effects of these policy changes. Legalization of recreational use will probably increase use in the long term, but the magnitude and timing of any increase is uncertain. It will be critical to monitor: cannabis use in household and high school surveys; cannabis sales; the number of cannabis plants legally produced; and the tetrahydrocannabinol (THC) content of cannabis. Indicators of cannabis-related harms that should be monitored include: car crash fatalities and injuries; emergency department presentations; presentations to addiction treatment services; and the prevalence of regular cannabis use among young people in mental health services and the criminal justice system. Plausible effects of legalizing recreational cannabis use in the United States include substantially reducing the price of cannabis and increasing heavy use and some types of cannabis-related harm among existing users. In the longer term it may also increase the number of new users. © 2016 Society for the Study of Addiction.

Topical Medical Cannabis: A New Treatment for Wound Pain-Three Cases of Pyoderma Gangrenosum.

PubMed

Maida, Vincent; Corban, Jason

2017-11-01

Pain associated with integumentary wounds is highly prevalent, yet it remains an area of significant unmet need within health care. Currently, systemically administered opioids are the mainstay of treatment. However, recent publications are casting opioids in a negative light given their high side effect profile, inhibition of wound healing, and association with accidental overdose, incidents that are frequently fatal. Thus, novel analgesic strategies for wound-related pain need to be investigated. The ideal methods of pain relief for wound patients are modalities that are topical, lack systemic side effects, noninvasive, self-administered, and display rapid onset of analgesia. Extracts derived from the cannabis plant have been applied to wounds for thousands of years. The discovery of the human endocannabinoid system and its dominant presence throughout the integumentary system provides a valid and logical scientific platform to consider the use of topical cannabinoids for wounds. We are reporting a prospective case series of three patients with pyoderma gangrenosum that were treated with topical medical cannabis compounded in nongenetically modified organic sunflower oil. Clinically significant analgesia that was associated with reduced opioid utilization was noted in all three cases. Topical medical cannabis has the potential to improve pain management in patients suffering from wounds of all classes. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

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

Cannabis in Chinese Medicine: Are Some Traditional Indications Referenced in Ancient Literature Related to Cannabinoids?

PubMed Central

Brand, E. Joseph; Zhao, Zhongzhen

2017-01-01

Cannabis sativa L. (Cannabaceae) has a long history of utilization as a fiber and seed crop in China, and its achenes (“seeds”) as well as other plant parts have been recorded in Chinese medical texts for nearly 2000 years. While the primary applications of cannabis in Chinese medicine center around the use of the achenes, ancient indications for the female inflorescence, and other plant parts include conditions such as pain and mental illness that are the subject of current research into cannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). However, little previous research has been conducted to analyze the Chinese medical literature in light of recent advances in the pharmacology and taxonomy of cannabis, and most of the relevant Chinese historical records have not yet been translated into Western languages to facilitate textual research. Furthermore, many key questions remain unresolved in the Chinese literature, including how various traditional drug names precisely correspond to different plant parts, as well as the implications of long-term selection for fiber-rich cultivars on the medical applications of cannabis in Chinese medicine. In this article, prominent historical applications of cannabis in Chinese medicine are chronologically reviewed, and indications found in ancient Chinese literature that may relate to cannabinoids such as CBD and Δ9-THC are investigated. PMID:28344554

Legalization, decriminalization & medicinal use of cannabis: a scientific and public health perspective.

PubMed

Svrakic, Dragan M; Lustman, Patrick J; Mallya, Ashok; Lynn, Taylor Andrea; Finney, Rhonda; Svrakic, Neda M

2012-01-01

Empirical and clinical studies clearly demonstrate significant adverse effects of cannabis smoking on physical and mental health as well as its interference with social and occupational functioning. These negative data far outweigh a few documented benefits for a limited set of medical indications, for which safe and effective alternative treatments are readily available. If there is any medical role for cannabinoid drugs, it lies with chemically defined compounds, not with unprocessed cannabis plant. Legalization or medical use of smoked cannabis is likely to impose significant public health risks, including an increased risk of schizophrenia, psychosis, and other forms of substance use disorders.

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.

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

[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

Hypoxia affects cellular responses to plant extracts.

PubMed

Liew, Sien-Yei; Stanbridge, Eric J; Yusoff, Khatijah; Shafee, Norazizah

2012-11-21

Microenvironmental conditions contribute towards varying cellular responses to plant extract treatments. Hypoxic cancer cells are known to be resistant to radio- and chemo-therapy. New therapeutic strategies specifically targeting these cells are needed. Plant extracts used in Traditional Chinese Medicine (TCM) can offer promising candidates. Despite their widespread usage, information on their effects in hypoxic conditions is still lacking. In this study, we examined the cytotoxicity of a series of known TCM plant extracts under normoxic versus hypoxic conditions. Pereskia grandifolia, Orthosiphon aristatus, Melastoma malabathricum, Carica papaya, Strobilanthes crispus, Gynura procumbens, Hydrocotyle sibthorpioides, Pereskia bleo and Clinacanthus nutans leaves were dried, blended into powder form, extracted in methanol and evaporated to produce crude extracts. Human Saos-2 osteosarcoma cells were treated with various concentrations of the plant extracts under normoxia or hypoxia (0.5% oxygen). 24h after treatment, an MTT assay was performed and the IC(50) values were calculated. Effect of the extracts on hypoxia inducible factor (HIF) activity was evaluated using a hypoxia-driven firefly luciferase reporter assay. The relative cytotoxicity of each plant extract on Saos-2 cells was different in hypoxic versus normoxic conditions. Hypoxia increased the IC(50) values for Pereskia grandifola and Orthosiphon aristatus extracts, but decreased the IC(50) values for Melastoma malabathricum and Carica papaya extracts. Extracts of Strobilanthes crispus, Gynura procumbens, Hydrocotyle sibthorpioides had equivalent cytotoxic effects under both conditions. Pereskia bleo and Clinacanthus nutans extracts were not toxic to cells within the concentration ranges tested. The most interesting result was noted for the Carica papaya extract, where its IC(50) in hypoxia was reduced by 3-fold when compared to the normoxic condition. This reduction was found to be associated with HIF

[Cannabis: Effects in the Central Nervous System. Therapeutic, societal and legal consequences].

PubMed

Rivera-Olmos, Víctor Manuel; Parra-Bernal, Marisela C

2016-01-01

The consumption of marijuana extracted from Cannabis sativa and indica plants involves an important cultural impact in Mexico. Their psychological stimulatory effect is widely recognized; their biochemical and molecular components interact with CB1 and CB2 (endocannabinoid system) receptors in various central nervous system structures (CNS) and immune cells. The psychoactive element Δ-9-tetrahydrocannabinol (THC) can be reproduced synthetically. Systematic reviews show evidence of therapeutic effectiveness of therapeutic marijuana only for certain symptoms of multiple sclerosis (spasticity, spasms and pain), despite attempts for its widespread use, including refractory childhood epilepsy. Evidence indicates significant adverse effects of smoked marijuana on the structure, functioning and brain connectivity. Cannabis exposure during pregnancy affects fetal brain development, potentially leading to later behavioral problems in children. Neuropsychological tests and advanced imaging techniques show involvement in the learning process in adolescents with substance use. Also, marijuana increases the cognitive impairment in patients with multiple sclerosis. Social and ethical consequences to legally free marijuana for recreational use may be deleterious transcendentally. The medicinal or psychoactive cannabinol no addictive effect requires controlled proven efficacy and safety before regulatory approval studies.

Training and Practices of Cannabis Dispensary Staff.

PubMed

Haug, Nancy A; Kieschnick, Dustin; Sottile, James E; Babson, Kimberly A; Vandrey, Ryan; Bonn-Miller, Marcel O

2016-01-01

Introduction: The proliferation of cannabis dispensaries within the United States has emerged from patient demand for the legalization of cannabis as an alternative treatment for a number of conditions and symptoms. Unfortunately, nothing is known about the practices of dispensary staff with respect to recommendation of cannabis strains/concentrations for specific patient ailments. To address this limitation, the present study assessed the training and practices of cannabis dispensary staff. Materials and Methods: Medical and nonmedical dispensary staff ( n =55) were recruited via e-mail and social media to complete an online survey assessing their demographic characteristics, dispensary features, patient characteristics, formal training, and cannabis recommendation practices. Results: Fifty-five percent of dispensary staff reported some formal training for their position, with 20% reporting medical/scientific training. A majority (94%) indicated that they provide specific cannabis advice to patients. In terms of strains, dispensary staff trended toward recommendations of Indica for anxiety, chronic pain, insomnia, nightmares, and Tourette's syndrome. They were more likely to recommend Indica and hybrid plants for post-traumatic stress disorder (PTSD)/trauma and muscle spasms. In contrast, staff were less likely to recommend Indica for depression; hybrid strains were most often recommended for amyotrophic lateral sclerosis (ALS). In terms of cannabinoid concentrations, dispensary staff were most likely to recommend a 1:1 ratio of delta-9-tetrahydrocannabinol (THC):cannabidiol (CBD) for patients suffering from anxiety, Crohn's disease, hepatitis C, and PTSD/trauma, while patients seeking appetite stimulation were most likely to be recommended THC. Staff recommended high CBD for arthritis and Alzheimer's disease and a high CBD or 1:1 ratio for ALS, epilepsy, and muscle spasms. Conclusions: Although many dispensary staff are making recommendations consistent with

Training and Practices of Cannabis Dispensary Staff

PubMed Central

Haug, Nancy A.; Kieschnick, Dustin; Sottile, James E.; Babson, Kimberly A.; Vandrey, Ryan; Bonn-Miller, Marcel O.

2016-01-01

Abstract Introduction: The proliferation of cannabis dispensaries within the United States has emerged from patient demand for the legalization of cannabis as an alternative treatment for a number of conditions and symptoms. Unfortunately, nothing is known about the practices of dispensary staff with respect to recommendation of cannabis strains/concentrations for specific patient ailments. To address this limitation, the present study assessed the training and practices of cannabis dispensary staff. Materials and Methods: Medical and nonmedical dispensary staff (n=55) were recruited via e-mail and social media to complete an online survey assessing their demographic characteristics, dispensary features, patient characteristics, formal training, and cannabis recommendation practices. Results: Fifty-five percent of dispensary staff reported some formal training for their position, with 20% reporting medical/scientific training. A majority (94%) indicated that they provide specific cannabis advice to patients. In terms of strains, dispensary staff trended toward recommendations of Indica for anxiety, chronic pain, insomnia, nightmares, and Tourette's syndrome. They were more likely to recommend Indica and hybrid plants for post-traumatic stress disorder (PTSD)/trauma and muscle spasms. In contrast, staff were less likely to recommend Indica for depression; hybrid strains were most often recommended for amyotrophic lateral sclerosis (ALS). In terms of cannabinoid concentrations, dispensary staff were most likely to recommend a 1:1 ratio of delta-9-tetrahydrocannabinol (THC):cannabidiol (CBD) for patients suffering from anxiety, Crohn's disease, hepatitis C, and PTSD/trauma, while patients seeking appetite stimulation were most likely to be recommended THC. Staff recommended high CBD for arthritis and Alzheimer's disease and a high CBD or 1:1 ratio for ALS, epilepsy, and muscle spasms. Conclusions: Although many dispensary staff are making recommendations consistent

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.

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.

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.

Evolution of the Cannabinoid and Terpene Content during the Growth of Cannabis sativa Plants from Different Chemotypes.

PubMed

Aizpurua-Olaizola, Oier; Soydaner, Umut; Öztürk, Ekin; Schibano, Daniele; Simsir, Yilmaz; Navarro, Patricia; Etxebarria, Nestor; Usobiaga, Aresatz

2016-02-26

The evolution of major cannabinoids and terpenes during the growth of Cannabis sativa plants was studied. In this work, seven different plants were selected: three each from chemotypes I and III and one from chemotype II. Fifty clones of each mother plant were grown indoors under controlled conditions. Every week, three plants from each variety were cut and dried, and the leaves and flowers were analyzed separately. Eight major cannabinoids were analyzed via HPLC-DAD, and 28 terpenes were quantified using GC-FID and verified via GC-MS. The chemotypes of the plants, as defined by the tetrahydrocannabinolic acid/cannabidiolic acid (THCA/CBDA) ratio, were clear from the beginning and stable during growth. The concentrations of the major cannabinoids and terpenes were determined, and different patterns were found among the chemotypes. In particular, the plants from chemotypes II and III needed more time to reach peak production of THCA, CBDA, and monoterpenes. Differences in the cannabigerolic acid development among the different chemotypes and between monoterpene and sesquiterpene evolution patterns were also observed. Plants of different chemotypes were clearly differentiated by their terpene content, and characteristic terpenes of each chemotype were identified.

Establishment of a New Drug Code for Marihuana Extract. Final rule.

PubMed

2016-12-14

The Drug Enforcement Administration is creating a new Administration Controlled Substances Code Number for "Marihuana Extract." This code number will allow DEA and DEA-registered entities to track quantities of this material separately from quantities of marihuana. This, in turn, will aid in complying with relevant treaty provisions. Under international drug control treaties administered by the United Nations, some differences exist between the regulatory controls pertaining to marihuana extract versus those for marihuana and tetrahydrocannabinols. The DEA has previously established separate code numbers for marihuana and for tetrahydrocannabinols, but not for marihuana extract. To better track these materials and comply with treaty provisions, DEA is creating a separate code number for marihuana extract with the following definition: "Meaning an extract containing one or more cannabinoids that has been derived from any plant of the genus Cannabis, other than the separated resin (whether crude or purified) obtained from the plant." Extracts of marihuana will continue to be treated as Schedule I controlled substances.

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.

The draft genome and transcriptome of Cannabis sativa

PubMed Central

2011-01-01

Background Cannabis sativa has been cultivated throughout human history as a source of fiber, oil and food, and for its medicinal and intoxicating properties. Selective breeding has produced cannabis plants for specific uses, including high-potency marijuana strains and hemp cultivars for fiber and seed production. The molecular biology underlying cannabinoid biosynthesis and other traits of interest is largely unexplored. Results We sequenced genomic DNA and RNA from the marijuana strain Purple Kush using shortread approaches. We report a draft haploid genome sequence of 534 Mb and a transcriptome of 30,000 genes. Comparison of the transcriptome of Purple Kush with that of the hemp cultivar 'Finola' revealed that many genes encoding proteins involved in cannabinoid and precursor pathways are more highly expressed in Purple Kush than in 'Finola'. The exclusive occurrence of Δ9-tetrahydrocannabinolic acid synthase in the Purple Kush transcriptome, and its replacement by cannabidiolic acid synthase in 'Finola', may explain why the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) is produced in marijuana but not in hemp. Resequencing the hemp cultivars 'Finola' and 'USO-31' showed little difference in gene copy numbers of cannabinoid pathway enzymes. However, single nucleotide variant analysis uncovered a relatively high level of variation among four cannabis types, and supported a separation of marijuana and hemp. Conclusions The availability of the Cannabis sativa genome enables the study of a multifunctional plant that occupies a unique role in human culture. Its availability will aid the development of therapeutic marijuana strains with tailored cannabinoid profiles and provide a basis for the breeding of hemp with improved agronomic characteristics. PMID:22014239

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

Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal Markets

PubMed Central

Vergara, Daniela; Bidwell, L. Cinnamon; Gaudino, Reggie; Torres, Anthony; Du, Gary; Ruthenburg, Travis C.; deCesare, Kymron; Land, Donald P.; Hutchison, Kent E.; Kane, Nolan C.

2017-01-01

As the most widely used illicit drug worldwide, and as a source of numerous under-studied pharmacologically-active compounds, a precise understanding of variability in psychological and physiological effects of Cannabis varieties is essential. The National Institute on Drug Abuse (NIDA) is designated as the sole legal producer of Cannabis for use in US research studies. We sought to compare the chemical profiles of Cannabis varieties that are available to consumers in states that have state-legalized use versus what is available to researchers interested in studying the plant and its effects. Our results demonstrate that the federally-produced Cannabis has significantly less variety and lower concentrations of cannabinoids than are observed in state-legal U.S. dispensaries. Most dramatically, NIDA’s varieties contain only 27% of the THC levels and as much as 11–23 times the Cannabinol (CBN) content compared to what is available in the state-legal markets. Research restricted to using the current range of federally-produced Cannabis thus may yield limited insights into the chemical, biological and pharmacological properties, and medical potential of material that is available in the state markets. Investigation is urgently needed on the full diversity of Cannabis chemotypes known to be available to the public. PMID:28422145

Seized cannabis seeds cultivated in greenhouse: A chemical study by gas chromatography-mass spectrometry and chemometric analysis.

PubMed

Mariotti, Kristiane de Cássia; Marcelo, Marcelo Caetano Alexandre; Ortiz, Rafael S; Borille, Bruna Tassi; Dos Reis, Monique; Fett, Mauro Sander; Ferrão, Marco Flôres; Limberger, Renata Pereira

2016-01-01

Cannabis sativa L. is cultivated in most regions of the world. In 2013, the Brazilian Federal Police (BFP) reported 220 tons of marijuana seized and about 800,000 cannabis plants eradicated. Efforts to eradicate cannabis production may have contributed to the development of a new form of international drug trafficking in Brazil: the sending of cannabis seeds in small amounts to urban centers by logistics postal. This new and increasing panorama of cannabis trafficking in Brazil, encouraged the chemical study of cannabis seeds cultivated in greenhouses by gas-chromatography coupled with mass spectrometry (GC-MS) associated with exploratory and discriminant analysis. Fifty cannabis seeds of different varieties and brands, seized by the BFP were cultivated under predefined conditions for a period of 4.5 weeks, 5.5 weeks, 7.5 weeks, 10 weeks and 12 weeks. Aerial parts were analyzed and cannabigerol, cannabinol, cannabidiol, cannabichromene Δ9-tetrahydrocannabinol (THC) and other terpenoids were detected. The chromatographic chemical profiles of the samples were significantly different, probably due to different variety, light exposition and age. THC content increased with the age of the plant, however, for other cannabinoids, this correlation was not observed. The chromatograms were plotted in a matrix with 50 rows (samples) and 3886 columns (abundance in a retention time) and submitted to PCA, HCA and PLS-DA after pretreatment (normalization, first derivative and autoscale). The PCA and HCA showed age separation between samples however it was not possible to verify the separation by varieties and brands. The PLS-DA classification provides a satisfactory prediction of plant age. Copyright © 2015 The Chartered Society of Forensic Sciences. Published by Elsevier Ireland Ltd. All rights reserved.

Interaction of Plant Extracts with Central Nervous System Receptors

PubMed Central

Lundstrom, Kenneth; Pham, Huyen Thanh; Dinh, Long Doan

2017-01-01

Background: Plant extracts have been used in traditional medicine for the treatment of various maladies including neurological diseases. Several central nervous system receptors have been demonstrated to interact with plant extracts and components affecting the pharmacology and thereby potentially playing a role in human disease and treatment. For instance, extracts from Hypericum perforatum (St. John’s wort) targeted several CNS receptors. Similarly, extracts from Piper nigrum, Stephania cambodica, and Styphnolobium japonicum exerted inhibition of agonist-induced activity of the human neurokinin-1 receptor. Methods: Different methods have been established for receptor binding and functional assays based on radioactive and fluorescence-labeled ligands in cell lines and primary cell cultures. Behavioral studies of the effect of plant extracts have been conducted in rodents. Plant extracts have further been subjected to mood and cognition studies in humans. Results: Mechanisms of action at molecular and cellular levels have been elucidated for medicinal plants in support of standardization of herbal products and identification of active extract compounds. In several studies, plant extracts demonstrated affinity to a number of CNS receptors in parallel indicating the complexity of this interaction. In vivo studies showed modifications of CNS receptor affinity and behavioral responses in animal models after treatment with medicinal herbs. Certain plant extracts demonstrated neuroprotection and enhanced cognitive performance, respectively, when evaluated in humans. Noteworthy, the penetration of plant extracts and their protective effect on the blood-brain-barrier are discussed. Conclusion: The affinity of plant extracts and their isolated compounds for CNS receptors indicates an important role for medicinal plants in the treatment of neurological disorders. Moreover, studies in animal and human models have confirmed a scientific basis for the application of medicinal

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 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

Levels of selected metals in leaves of Cannabis sativa L. cultivated in Ethiopia.

PubMed

Zerihun, Agalu; Chandravanshi, Bhagwan Singh; Debebe, Ayalew; Mehari, Bewketu

2015-01-01

Cannabis sativa L. is one of the illicit drug bearing plants. Cannabis products are the most widely trafficked drugs worldwide. The highest levels of cannabis production in the world take place in the African continent. A small volume of cannabis is produced in rural areas of Ethiopia, of which a small portion is exported to neighboring countries and the majority is consumed at home. The literature survey revealed that there is no report on the metal contents in cannabis cultivated in Ethiopia. The main objective of this study is to determine the level of selected metals in leaves of Cannabis sativa L. cultivated in Ethiopia. Cannabis sativa L. samples were collected from Metema (Amhara Region), Mekelle (Tigray Region), Sheshemene (Oromia Region) and Butajira (South Nations Nationality and Peoples (SNNP) Region) of Ethiopia. After proper sample pretreatment, the volumes of reagents used, digestion temperature and digestion time were optimized and using the optimized conditions the levels of metals were determined by flame atomic absorption spectrometry. The accuracy of the optimized procedure was evaluated by analyzing the digest of the spiked samples with standard solution and the percentage recoveries varied from 88 to 103%. The levels of metals determined (µg/g dry weight) were in the ranges Ca (657-1,511), Zn (321-380), Ni (124-172), Cu (122-176), Cd (3-10), Pb (8-10), and Cr (4-8). Zn was with the highest concentration among trace metals. A statistical analysis of variance (ANOVA) at 95% confidence level indicated that there is a significant difference in the levels of all the metals between the four sample means except Pb. The results indicate that the content of Pb and Cd exceeds the permissible amount for medicinal plants which form the raw materials for the finished products set by World Health Organization (WHO).

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.

A review of the cultivation and processing of cannabis (Cannabis sativa L.) for production of prescription medicines in the UK.

PubMed

Potter, David J

2014-01-01

The quality demands of the pharmaceutical industry require prescription medicines to be consistent in their active ingredient content. Achieving this, using raw cannabis as a feedstock, is especially challenging. The plant material is extremely inhomogeneous, and the ratios of active ingredients are affected by a range of factors. These include the genetics of the plant, the growing and storage conditions, the state of maturity at harvest, and the methods used to process and formulate the material. The reasons for this variability are described, with particular emphasis on the botanical considerations. To produce the complex botanical medicine Sativex®, which contains the cannabinoids Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) and a range of other ingredients, GW Pharmaceuticals had to manage these variables. This medicine, for the treatment of spasticity due to multiple sclerosis, is the first cannabis-based medicine to be approved in the UK. The company's methodology for producing this and other chemotypes is described. Copyright © 2013 John Wiley & Sons, Ltd.

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.

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.

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.

The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review.

PubMed

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

2017-09-05

Cannabis is increasingly available for the treatment of chronic pain, yet its efficacy remains uncertain. To review the benefits of plant-based cannabis preparations for treating chronic pain in adults and the harms of cannabis use in chronic pain and general adult populations. MEDLINE, Cochrane Database of Systematic Reviews, and several other sources from database inception to March 2017. Intervention trials and observational studies, published in English, involving adults using plant-based cannabis preparations that reported pain, quality of life, or adverse effect outcomes. Two investigators independently abstracted study characteristics and assessed study quality, and the investigator group graded the overall strength of evidence using standard criteria. From 27 chronic pain trials, there is low-strength evidence that cannabis alleviates neuropathic pain but insufficient evidence in other pain populations. According to 11 systematic reviews and 32 primary studies, harms in general population studies include increased risk for motor vehicle accidents, psychotic symptoms, and short-term cognitive impairment. Although adverse pulmonary effects were not seen in younger populations, evidence on most other long-term physical harms, in heavy or long-term cannabis users, or in older populations is insufficient. Few methodologically rigorous trials; the cannabis formulations studied may not reflect commercially available products; and limited applicability to older, chronically ill populations and patients who use cannabis heavily. Limited evidence suggests that cannabis may alleviate neuropathic pain in some patients, but insufficient evidence exists for other types of chronic pain. Among general populations, limited evidence suggests that cannabis is associated with an increased risk for adverse mental health effects. U.S. Department of Veterans Affairs. (PROSPERO: CRD42016033623).

Initiation of vaporizing cannabis: Individual and social network predictors in a longitudinal study of young adults.

PubMed

Cassidy, Rachel N; Meisel, Matthew K; DiGuiseppi, Graham; Balestrieri, Sara; Barnett, Nancy P

2018-05-19

A trend has recently emerged of individuals using electronic nicotine delivery systems (ENDS) or similar devices to vaporize cannabis, either in the form of high-potency THC concentrates or cannabis plant material. Peer use is central to the adoption of substance use behaviors in young adulthood, but little is known about peer influence for initiating cannabis vaping. A longitudinal investigation of first-year college students (N = 1313) using social network methods was conducted to determine the prevalence of vaping cannabis, differences in networks between individuals who initiate vaping cannabis, and predictors of initiation of vaping cannabis across two time points. The surveys were available for two weeks beginning in the sixth week of each semester. We found that 9.4% vaped in their lifetime but not since the first survey, 7.5% vaped in their lifetime and since the first survey, and 5.9% reported vaping cannabis at the second survey. Lifetime cannabis use, lifetime ENDS use, and number of peers who initiated vaping cannabis from Time 1 to Time 2 were significantly associated with increased odds of the initiation of vaping cannabis; the number of any-cannabis-using or any-ENDS-using peers was not associated with increased odds of initiating vaping cannabis. Individuals with the greatest risk of initiation of vaping cannabis during the first year of college are those with a prior history of other cannabis use and ENDS use and who have peers in their network who initiate cannabis vaping. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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.

[CANNABIS AND GLAUCOMA: AN ANCIENT LEGEND OR A NOVEL THERAPEUTIC HORIZON?].

PubMed

Mathalone, Nurit; Wolf, Alvit; Geyer, Orna

2015-06-01

Glaucoma causes damage to the optic nerve and compromises the visual field. The main risk factor of the disease is the level of the intra-ocular pressure. Therapeutic options include medical and surgical treatment, aimed to lower the intra-ocular pressure. Consumption of the cannabis plant (Cannabis Satival has been known since ancient times. It can be consumed orally, topically, intra-venous or by inhalation. The main active ingredient of cannabis is THC (Tetra-Hydro-Cannabinol). One of THC's reported effects is the reduction of intra-ocular pressure. Several studies have demonstrated temporary intra-ocular pressure decrease in both healthy subjects and glaucoma patients following topical application or systemic consumption. The effect was a short term one. It was followed by the development of resistance to the drug after prolonged intake and it was also accompanied by topical and systemic side effects. Cannabis may be considered as a therapeutic option in glaucoma. Its limited effect, development of resistance, acquired side effects and the accompanying psycho-active influence limit its advantage and cause its efficacy to be dubious. Therefore, cannabis treatment for glaucoma currently seems impractical and is not recommended by either the Israeli or the American glaucoma societies.

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

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.

Molecular analysis of genetic fidelity in Cannabis sativa L. plants grown from synthetic (encapsulated) seeds following in vitro storage.

PubMed

Lata, Hemant; Chandra, Suman; Techen, Natascha; Khan, Ikhlas A; ElSohly, Mahmoud A

2011-12-01

The increasing utilization of synthetic (encapsulated) seeds for germplasm conservation and propagation necessitates the assessment of genetic stability of conserved propagules following their plantlet conversion. We have assessed the genetic stability of synthetic seeds of Cannabis sativa L. during in vitro multiplication and storage for 6 months at different growth conditions using inter simple sequence repeat (ISSR) DNA fingerprinting. Molecular analysis of randomly selected plants from each batch was conducted using 14 ISSR markers. Of the 14 primers tested, nine produced 40 distinct and reproducible bands. All the ISSR profiles from in vitro stored plants were monomorphic and comparable to the mother plant which confirms the genetic stability among the clones. GC analysis of six major cannabinoids [Δ(9)-tetrahydrocannabinol, tetrahydrocannabivarin, cannabidiol, cannabichromene, cannabigerol and cannabinol] showed homogeneity in the re-grown clones and the mother plant with insignificant differences in cannabinoids content, thereby confirming the stability of plants derived from synthetic seeds following 6 months storage. © Springer Science+Business Media B.V. 2011

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.

Cannabis in cancer care.

PubMed

Abrams, D I; Guzman, M

2015-06-01

Cannabis has been used in medicine for thousands of years prior to achieving its current illicit substance status. Cannabinoids, the active components of Cannabis sativa, mimic the effects of the endogenous cannabinoids (endocannabinoids), activating specific cannabinoid receptors, particularly CB1 found predominantly in the central nervous system and CB2 found predominantly in cells involved with immune function. Delta-9-tetrahydrocannabinol, the main bioactive cannabinoid in the plant, has been available as a prescription medication approved for treatment of cancer chemotherapy-induced nausea and vomiting and anorexia associated with the AIDS wasting syndrome. Cannabinoids may be of benefit in the treatment of cancer-related pain, possibly synergistic with opioid analgesics. Cannabinoids have been shown to be of benefit in the treatment of HIV-related peripheral neuropathy, suggesting that they may be worthy of study in patients with other neuropathic symptoms. Cannabinoids have a favorable drug safety profile, but their medical use is predominantly limited by their psychoactive effects and their limited bioavailability. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil by ultra-high performance liquid chromatography tandem mass spectrometry.

PubMed

Pacifici, Roberta; Marchei, Emilia; Salvatore, Francesco; Guandalini, Luca; Busardò, Francesco Paolo; Pichini, Simona

2017-08-28

Cannabis has been used since ancient times to relieve neuropathic pain, to lower intraocular pressure, to increase appetite and finally to decrease nausea and vomiting. The combination of the psychoactive cannabis alkaloid Δ9-tetrahydrocannabinol (THC) with the non-psychotropic alkaloids cannabidiol (CBD) and cannabinol (CBN) demonstrated a higher activity than THC alone. The Italian National Institute of Health sought to establish conditions and indications on how to correctly use nationally produced cannabis to guarantee therapeutic continuity in individuals treated with medical cannabis. The evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil was conducted using an easy and fast ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay. Extraction efficiency of oil was significantly higher than that of water with respect to the different cannabinoids. This was especially observed in the case of the pharmacologically active THC, CBD and their acidic precursors. Fifteen minutes boiling was sufficient to achieve the highest concentrations of cannabinoids in the cannabis tea solutions. At ambient temperature, a significant THC and CBD decrease to 50% or less of the initial concentration was observed over 3 and 7 days, respectively. When refrigerated at 4 °C, similar decreasing profiles were observed for the two compounds. The cannabinoids profile in cannabis oil obtained after pre-heating the flowering tops at 145 °C for 30 min in a static oven resulted in a complete decarboxylation of cannabinoid acids CBDA and THCA-A. Nevertheless, it was apparent that heat not only decarboxylated acidic compounds, but also significantly increased the final concentrations of cannabinoids in oil. The stability of cannabinoids in oil samples was higher than that in tea samples since the maximum decrease (72% of initial concentration) was observed in THC coming from unheated flowering

Study on extraction process and activity of plant polysaccharides

NASA Astrophysics Data System (ADS)

Ma, Xiaogen; Wang, Xiaojing; Fan, Shuangli; Chen, Jiezhong

2017-10-01

Recent studies have shown that plant polysaccharides have many pharmacological activities, such as hypoglycemic, anti-inflammatory and tumor inhibition. The pharmacological activities of plant polysaccharides were summarized. The extraction methods of plant polysaccharides were discussed. Finally, the extraction process of Herba Taraxaci polysaccharides was optimized by ultrasonic assisted extraction. Through single factor experiments and orthogonal experiment to optimize the optimum extraction process from dandelion polysaccharide, optimum conditions of dandelion root polysaccharide by ultrasonic assisted extraction method for ultrasonic power 320W, temperature 80°C, extraction time 40min, can get higher dandelion polysaccharide extract.

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.

Predicting cannabis cultivation on national forests using a rational choice framework

Treesearch

Frank H. Koch; Jeff Prestemon; Geoffrey H. Donovan; Everett A. Hinkley; John M. Chase

2016-01-01

Government agencies in the United States eradicated 10.3 million cannabis plants in 2010. Most (94%) of these plants were outdoor-grown, and 46% of those were discovered on federal lands, primarily on national forests in California, Oregon, and Washington. We developed models that reveal how drug markets, policies, and environmental...

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

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

Development of a new extraction technique and HPLC method for the analysis of non-psychoactive cannabinoids in fibre-type Cannabis sativa L. (hemp).

PubMed

Brighenti, Virginia; Pellati, Federica; Steinbach, Marleen; Maran, Davide; Benvenuti, Stefania

2017-09-05

The present work was aimed at the development and validation of a new, efficient and reliable technique for the analysis of the main non-psychoactive cannabinoids in fibre-type Cannabis sativa L. (hemp) inflorescences belonging to different varieties. This study was designed to identify samples with a high content of bioactive compounds, with a view to underscoring the importance of quality control in derived products as well. Different extraction methods, including dynamic maceration (DM), ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE) and supercritical-fluid extraction (SFE) were applied and compared in order to obtain a high yield of the target analytes from hemp. Dynamic maceration for 45min with ethanol (EtOH) at room temperature proved to be the most suitable technique for the extraction of cannabinoids in hemp samples. The analysis of the target analytes in hemp extracts was carried out by developing a new reversed-phase high-performance liquid chromatography (HPLC) method coupled with diode array (UV/DAD) and electrospray ionization-mass spectrometry (ESI-MS) detection, by using an ion trap mass analyser. An Ascentis Express C 18 column (150mm×3.0mm I.D., 2.7μm) was selected for the HPLC analysis, with a mobile phase composed of 0.1% formic acid in both water and acetonitrile, under gradient elution. The application of the fused-core technology allowed us to obtain a significant improvement of the HPLC performance compared with that of conventional particulate stationary phases, with a shorter analysis time and a remarkable reduction of solvent usage. The analytical method optimized in this study was fully validated to show compliance with international requirements. Furthermore, it was applied to the characterization of nine hemp samples and six hemp-based pharmaceutical products. As such, it was demonstrated to be a very useful tool for the analysis of cannabinoids in both the plant material and its derivatives for

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.

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

Patterns of use of medical cannabis among Israeli cancer patients: a single institution experience.

PubMed

Waissengrin, Barliz; Urban, Damien; Leshem, Yasmin; Garty, Meital; Wolf, Ido

2015-02-01

The use of the cannabis plant (Cannabis sativa L.) for the palliative treatment of cancer patients has been legalized in multiple jurisdictions including Israel. Yet, not much is currently known regarding the efficacy and patterns of use of cannabis in this setting. To analyze the indications for the administration of cannabis among adult Israeli cancer patients and evaluate its efficacy. Efficacy and patterns of use of cannabis were evaluated using physician-completed application forms, medical files, and a detailed questionnaire in adult cancer patients treated at a single institution. Of approximately 17,000 cancer patients seen, 279 (<1.7%) received a permit for cannabis from an authorized institutional oncologist. The median age of cannabis users was 60 years (range 19-93 years), 160 (57%) were female, and 234 (84%) had metastatic disease. Of 151 (54%) patients alive at six months, 70 (46%) renewed their cannabis permit. Renewal was more common among younger patients and those with metastatic disease. Of 113 patients alive and using cannabis at one month, 69 (61%) responded to the detailed questionnaire. Improvement in pain, general well-being, appetite, and nausea were reported by 70%, 70%, 60%, and 50%, respectively. Side effects were mild and consisted mostly of fatigue and dizziness. Cannabis use is perceived as highly effective by some patients with advanced cancer and its administration can be regulated, even by local authorities. Additional studies are required to evaluate the efficacy of cannabis as part of the palliative treatment of cancer patients. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

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, pesticides and conflicting laws: the dilemma for legalized States and implications for public health.

PubMed

Stone, Dave

2014-08-01

State laws on the legalization of medical and recreational cannabis are rapidly evolving. Similar to other crops, cannabis is susceptible to multiple pests during cultivation. Growers have an economic incentive to produce large yields and high quality plants, and may resort to pesticides to achieve these outcomes. Currently, there are no pesticides registered for cannabis in the United States, given its illegal status by the federal government. This discrepancy creates a regulatory vacuum and dilemma for States with legal medical and recreational cannabis that seek to balance lawful compliance with pesticides and worker or public health. Pesticide use presents occupational safety issues that can be mitigated through established worker protection measures. The absence of approved products for cannabis may result in consumer exposures to otherwise more hazardous pesticides or higher residue levels. While many legal and scientific hurdles exist to register conventional pesticides for use on cannabis, legalized States have explored other opportunities to leverage the present regulatory infrastructure. Stakeholder engagement and outreach to the cannabis industry from credible sources could mitigate pesticide misuse and harm. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

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

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

[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.

75 FR 67054 - Listing of Approved Drug Products Containing Dronabinol in Schedule III

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-01

... dronabinol extracted from Cannabis sativa (i.e. naturally-derived), is identical to synthetically-produced... psychoactive component of the cannabis plant (marijuana). THC, as a general category, is listed in schedule I... capsule form containing natural dronabinol (derived from the cannabis plant) or synthetic dronabinol...

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.

Current Perspectives on Biotechnological Cannabinoid Production in Plants.

PubMed

Schachtsiek, Julia; Warzecha, Heribert; Kayser, Oliver; Stehle, Felix

2018-03-01

The plant Cannabis sativa contains a number of psychoactive chemical compounds, the cannabinoids, which possess a significant pharmaceutical potential. Recently, the usage of Cannabis for medicinal purposes was legalized in many countries. Thus, the study on the influence of different cannabinoids in combination with other Cannabis -derived compounds with respect to the treatment of various diseases becomes increasingly important. Besides the production of distinct cannabinoids in a heterologous host, like tobacco or yeast, transgenic Cannabis plants would be a suitable alternative to modify and therefore optimize the cannabinoid profile. This perspective highlights the current efforts on Cannabis cell culture systems, in vitro propagation, and transformation of the plant and reveals the resulting opportunities concerning biotechnological production of cannabinoids. Furthermore, alternative platform organisms for the heterologous production of cannabinoids, like tobacco, are considered and evaluated. Georg Thieme Verlag KG Stuttgart · New York.

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.

Antileishmanial Potential of Tropical Rainforest Plant Extracts

PubMed Central

Monzote, Lianet; Piñón, Abel; Setzer, William N.

2014-01-01

A total of 115 different plant extracts from our collection, representing 96 plant species, have been evaluated for in vitro antileishmanial activity against L. amazonensis promastigotes. In addition, the extracts were screened for cytotoxic activity against BALB/c mouse macrophages in order to assess a selectivity index. Crude extracts that showed a selectivity index (CC50 for macrophage / IC50 for promastigotes) ≥ 5 or with IC50 < 12.5 μg/mL against promastigotes, a total of 28 extracts, were further screened for anti-amastigote activity. A total of 25 extracts showed promising activity against L. amazonensis promastigotes with low cytotoxic activity. Ten of these extracts showed selectivity indices, (CC50 for macrophages / IC50 for amastigotes) greater than 10 and are considered “hits”, worthy candidates for further phytochemical exploration: Conostegia xalapensis methanol bark extract, Endiandra palmerstonii bark extract, Eugenia monteverdensis acetone bark extract, Eugenia sp. “fine leaf” acetone bark extract, Exothea paniculata chloroform bark extract, Mallotus paniculatus ethanol bark extract, Matelea pseudobarbata ethanol extract, Quercus insignis ethanol bark extract, Sassafras albidum dichloromethane bark extract, and Stemmadenia donnell-smithii acetone bark extract. PMID:28933376

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

Legal issues for German-speaking cannabis growers. Results from an online survey.

PubMed

Werse, Bernd

2016-02-01

Cannabis prohibition can generally be regarded as the main driver for home growing of marijuana. In this paper, I discuss the impact of drug prohibition on cannabis cultivators from the three German-speaking countries: Germany, Austria and Switzerland. In particular, this refers to the questions; how illicitness influences motivations for growing; which precautionary measures are taken against the risk of discovery; how penal consequences differ in the three countries and how these aspects are linked to each other. The results come from a sample of 1578 respondents from the German-language online survey conducted following the International Cannabis Cultivation Questionnaire (ICCQ). The survey was carried out in late 2012 and early 2013. While most of the reasons for growing cannabis relate to avoiding negative consequences of prohibition, the illicitness of cannabis also plays a major role for concern about the cultivation activities as well as measures to avoid negative consequences. Swiss growers are less worried about their activity compared to respondents from Germany or Austria. The results confirm the notion that the illicitness of cannabis is the main drive for the private cultivation of the plant. At the same time, prohibition is the principal reason for concern regarding the growing activity. The severity of possible sentences seems to be linked to the degree of concern and precautionary measures. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Is cannabis treatment for anxiety, mood, and related disorders ready for prime time?

PubMed

Turna, Jasmine; Patterson, Beth; Van Ameringen, Michael

2017-11-01

Anxiety and related disorders are the most common mental conditions affecting the North American population. Despite their established efficacy, first-line antidepressant treatments are associated with significant side effects, leading many afflicted individuals to seek alternative treatments. Cannabis is commonly viewed as a natural alternative for a variety of medical and mental health conditions. Currently, anxiety ranks among the top five medical symptoms for which North Americans report using medical marijuana. However, upon careful review of the extant treatment literature, the anxiolytic effects of cannabis in clinical populations are surprisingly not well-documented. The effects of cannabis on anxiety and mood symptoms have been examined in healthy populations and in several small studies of synthetic cannabinoid agents but there are currently no studies which have examined the effects of the cannabis plant on anxiety and related disorders. In light of the rapidly shifting landscape regarding the legalization of cannabis for medical and recreational purposes, it is important to highlight the significant disconnect between the scientific literature, public opinion, and related policies. The aim of this article is to provide a comprehensive review of the current cannabis treatment literature, and to identify the potential for cannabis to be used as a therapeutic intervention for anxiety, mood, and related disorders. Searches of five electronic databases were conducted (PubMed, MEDLINE, Web of Science, PsychINFO, and Google Scholar), with the most recent in February 2017. The effects of cannabis on healthy populations and clinical psychiatric samples will be discussed, focusing primarily on anxiety and mood disorders. © 2017 Wiley Periodicals, Inc.

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.

Building smart cannabis policy from the science up.

PubMed

Weiss, Susan R B; Howlett, Katia D; Baler, Ruben D

2017-04-01

Social attitudes and cultural norms around the issue of substance abuse are shifting rapidly around the world, leading to complex and unpredictable consequences. On the positive side, efforts to more intensely disseminate the scientific evidence for the many connections between chronic substance use and the emergence of measurable and discrete brain dysfunctions, has ushered in an evolving climate of acceptance and a new era of improved access to more effective interventions, at least in the United States. On the negative side, there has been a steady erosion in the public perception of the harms associated with the use of popular drugs, especially cannabis. This worrisome trend has sprouted at the convergence of several forces that have combined, more or less fortuitously, to effectively change long-standing policies away from prohibition and toward decriminalization or legalization. These forces include the outsized popularity of the cannabis plant among recreational users, the unflagging campaign by corporate lobbyists and patient advocates to mainstream its medicinal use, and the honest realization in some quarters of the deleterious impact of the drug war and its draconian cannabis laws, in particular, on society's most vulnerable populations. Updating drug policies is a desirable goal, and significant changes may indeed be warranted. However, there is a real concern when policy changes are hurriedly implemented without the required input from the medical, scientific, or policy research communities. Regardless of how well intentioned, such initiatives are bound to magnify the potential for unintended adverse consequences in the form of far ranging health and social costs. To minimize this risk, science must be front and center in this important policy debate. Here, we review the state of the science on cannabis and cannabinoid health effects, both adverse and therapeutic. We focus on the prevalence of use in different populations, the mechanisms by which

“Hallucinations” Following Acute Cannabis Dosing: A Case Report and Comparison to Other Hallucinogenic Drugs

PubMed Central

Barrett, Frederick S.; Schlienz, Nicolas J.; Lembeck, Natalie; Waqas, Muhammad; Vandrey, Ryan

2018-01-01

Abstract Introduction: Cannabis has been historically classified as a hallucinogen. However, subjective cannabis effects do not typically include hallucinogen-like effects. Empirical reports of hallucinogen-like effects produced by cannabis in controlled settings, particularly among healthy research volunteers, are rare and have mostly occurred after administration of purified Δ-9 tetrahydrocannabinol (THC) rather than whole plant cannabis. Methods: The case of a healthy 30-year-old male who experienced auditory and visual hallucinations in a controlled laboratory study after inhaling vaporized cannabis that contained 25 mg THC (case dose) is presented. Ratings on the Hallucinogen Rating Scale (HRS) following the case dose are compared with HRS ratings obtained from the participant after other doses of cannabis and with archival HRS data from laboratory studies involving acute doses of cannabis, psilocybin, dextromethorphan (DXM), and salvinorin A. Results: Scores on the Volition subscale of the HRS were greater for the case dose than for the maximum dose administered in any other comparison study. Scores on the Intensity and Perception subscales were greater for the case dose than for the maximum dose of cannabis, psilocybin, or salvinorin A. Scores on the Somaesthesia subscale were greater for the case dose than for the maximum dose of DXM, salvinorin A, or cannabis. Scores on the Affect and Cognition subscales for the case dose were significantly lower than for the maximum doses of psilocybin and DXM. Conclusion: Acute cannabis exposure in a healthy adult male resulted in self-reported hallucinations that rated high in magnitude on several subscales of the HRS. However, the hallucinatory experience in this case was qualitatively different than that typically experienced by participants receiving classic and atypical hallucinogens, suggesting that the hallucinatory effects of cannabis may have a unique pharmacological mechanism of action. This type of adverse

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

"The difference is in the tomato at the end": Understanding the motivations and practices of cannabis growers operating within Belgian Cannabis Social Clubs.

PubMed

Pardal, Mafalda

2018-03-11

In Belgium, Cannabis Social Clubs (CSCs) collectively organize the cultivation and distribution of cannabis for the personal use of their members. In this paper we seek to improve understanding of the motivations and practices of cannabis growers operating within CSCs, shedding light on the cultivation process. We draw on data gathered through face-to-face semi-structured interviews with the directors of seven active Belgian CSCs (n = 21) and CSC growers (n = 23). These data are complemented by additional fieldwork and a review of policies relating to CSCs', including bylaws and growing protocols. The Belgian CSCs rely on single and multiple in-house grower arrangements. Most CSC growers had been cultivating cannabis prior to joining their current CSC, albeit growing in different contexts (non-commercial and commercial). The CSC growers discussed both ideological and pragmatic motives for operating within a CSC. Cultivation took place indoors and followed organic practices. Despite their small-scale (20 plants on average), the grow sites used specialized equipment. The growers reported receiving financial compensation to cover production costs. This paper offers new insights into a particular sector of domestic cannabis cultivation - CSC growers and their practices within those collectives - which has not been studied previously. The Belgian CSCs have decentralized production among small-scale grow sites, at a size comparable to that found in other small-scale cultivation studies. In terms of motivations and practices, CSC growers share some features typically ascribed to small-scale cannabis cultivators. At the same time, CSC growers seemed particularly engaged with the CSC model and willing to adhere to the (self-)regulated practices developed by the organizations. This had implications for the way cultivation was organized and for the role of the grower within the CSC. Copyright © 2018 Elsevier B.V. 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.

Machine vision extracted plant movement for early detection of plant water stress.

PubMed

Kacira, M; Ling, P P; Short, T H

2002-01-01

A methodology was established for early, non-contact, and quantitative detection of plant water stress with machine vision extracted plant features. Top-projected canopy area (TPCA) of the plants was extracted from plant images using image-processing techniques. Water stress induced plant movement was decoupled from plant diurnal movement and plant growth using coefficient of relative variation of TPCA (CRV[TPCA)] and was found to be an effective marker for water stress detection. Threshold value of CRV(TPCA) as an indicator of water stress was determined by a parametric approach. The effectiveness of the sensing technique was evaluated against the timing of stress detection by an operator. Results of this study suggested that plant water stress detection using projected canopy area based features of the plants was feasible.

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.

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

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

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.

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.

Plant extracts in the control of Phytophthora cryptogea.

PubMed

Orlikowski, L B

2001-01-01

Grapefruit extract at dose 40 micrograms/cm3 inhibited Phytophtora cryptogea linear growth about 50% and almost completely suppressed zoosporangia formation. Drenching of gerbera plants with the extract at dose 165 micrograms/cm3 reduced population density of the pathogen about 70% and this high efficacy was noted at least one month after application. Treatment of gerberas with grapefruit extract resulted in protection of about 50% of plants against the pathogen. Biological activity of purple coneflower extract was lower than extract from grapefruit. Significant decrease of population density of the pathogen during the first 5 days and increase of gerbera healthy stand was observed, however, in peat treated with that extract.

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.

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.

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

Ultrahigh pressure extraction of bioactive compounds from plants-A review.

PubMed

Xi, Jun

2017-04-13

Extraction of bioactive compounds from plants is one of the most important research areas for pharmaceutical and food industries. Conventional extraction techniques are usually associated with longer extraction times, lower yields, more organic solvent consumption, and poor extraction efficiency. A novel extraction technique, ultrahigh pressure extraction, has been developed for the extraction of bioactive compounds from plants, in order to shorten the extraction time, decrease the solvent consumption, increase the extraction yields, and enhance the quality of extracts. The mild processing temperature of ultrahigh pressure extraction may lead to an enhanced extraction of thermolabile bioactive ingredients. A critical review is conducted to introduce the different aspects of ultrahigh pressure extraction of plants bioactive compounds, including principles and mechanisms, the important parameters influencing its performance, comparison of ultrahigh pressure extraction with other extraction techniques, advantages, and disadvantages. The future opportunities of ultrahigh pressure extraction are also discussed.