Journal of cannabis research最新文献

Background: Most studies examining the simultaneous use of cannabis with other drugs have focused on cannabis and alcohol, with fewer studies examining simultaneous use of cannabis with other drugs. The United States is currently experiencing an upward trend in psychedelic use and there is an increasing need to characterize cannabis and psychedelic drug interactions to best inform public health recommendations.

Materials and methods: A mixed methods field study design was used to survey participants (N = 128) on their lifetime co-use of cannabis with other drugs. Participants who reported lifetime co-use of cannabis and psychedelics (N = 63) were then asked open-ended questions about their most recent simultaneous co-use experience (i.e., how cannabis enhanced their psychedelic experience and whether they experienced any adverse reactions). We conducted a thematic analysis of responses describing how cannabis enhanced the psychedelic experience (N = 54). However, due to low response rate for participants reporting an adverse reaction (N = 7, 11.1%), responses to this question were not analyzed thematically and are instead presented individually.

Results: Themes included tension reduction and balancing of drug effects (N = 27, 50%), enhancement to psychological processes (N = 11, 20.4%), intensified psychedelic drug effects (N = 12, 22.2%), enhanced psychedelic come-down experience (N = 8, 14.8%), and overall ambiguous enhancement (N = 7, 13%). Among participants reporting an adverse reaction, individual responses included increased anxiety and intensity of the experience, decreased sociability, increased negative affect, sleepiness, disassociation, and confusion.

Conclusion: Additional research is warranted to better characterize cannabis and psychedelic drug interactions to best inform public health recommendations.

Background: The belief that cannabis has analgesic and anti-inflammatory properties continues to attract patients with chronic musculoskeletal (MSK) pain towards its use. However, the role that cannabis will play in the management of chronic MSK pain remains to be determined. This study examined 1) the rate, patterns of use, and self-reported efficacy of cannabis use among patients with chronic MSK pain and 2) the interest and potential barriers to cannabis use among patients with chronic MSK pain not currently using cannabis.

Methods: Self-reported cannabis use and perceived efficacy were prospectively collected from chronic MSK pain patients presenting to the Orthopaedic Clinic at the University Health Network, Toronto, Canada. The primary dependent variable was current or past use of cannabis to manage chronic MSK pain; bivariate and multivariable logistic regression were used to identify patient characteristics independently associated with this outcome. Secondary outcomes were summarized descriptively, including self-perceived efficacy among cannabis users, and interest as well as barriers to cannabis use among cannabis non-users.

Results: The sample included 629 patients presenting with chronic MSK pain (mean age: 56±15.7 years; 56% female). Overall, 144 (23%) reported past or present cannabis use to manage their MSK pain, with 63.7% perceiving cannabis as very or somewhat effective and 26.6% considering it as slightly effective. The strongest predictor of cannabis use in this study population was a history of recreational cannabis use (OR 12.7, p<0.001). Among cannabis non-users (N=489), 65% expressed interest in using cannabis to manage their chronic MSK pain, but common barriers to use included lack of knowledge regarding access, use and evidence, and stigma.

Conclusions: One in five patients presenting to an orthopaedic surgeon with chronic MSK pain are using or have used cannabis with the specific intent to manage their pain, and most report it to be effective. Among non-users, two-thirds reported an interest in using cannabis to manage their MSK pain, but common barriers to use existed. Future double-blind placebo-controlled trials are required to understand if this reported efficacy is accurate, and what role, if any, cannabis may play in the management of chronic MSK pain.

Background: Cannabidiol is highly bound to plasma proteins. Changes in its protein binding can lead to altered unbound plasma concentrations and result in alteration of pharmacological activity of cannabidiol-containing medications. This research has assessed non-linearity of cannabidiol plasma protein binding and the potential effect of tizoxanide on the binding.

Method: Cannabidiol protein binding was evaluated by ultrafiltration technique. Human plasma was spiked with cannabidiol stock solution to produce samples of various concentrations. For interaction study potential interactant tizoxanide was added in each sample. All samples were processed through Amicon Micropartition system and analyzed by HPLC.

Results: The study has detected cannabidiol binding to borosilicate glass (9%) and polyethylene plastics (15%). In the interaction study the mean protein unbound fraction of cannabidiol was 0.05 (5%), indicating no binding interaction between cannabidiol and tizoxanide since cannabidiol unbound fraction without tizoxanide was also 5%. The cannabidiol fraction unbound was more than 2-fold greater at high concentrations compared to low concentrations.

Conclusion: a). At high concentrations cannabidiol plasma protein binding is non-linear. The non-linearity can affect elimination and medicinal effect of cannabidiol drugs. b). Borosilicate and polyethylene containers should be avoided in formulation, packing and administration of cannabidiol-containing medicines to guarantee correct doses. c). Cannabidiol medications can be co-administered with tizoxanide without caution.

Background: Cannabis has been shown to impact driving due to changes produced by delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis. Current legal thresholds for blood THC while driving are based predominantly on evidence utilizing smoked cannabis. It is known that levels of THC in blood are lower after eating cannabis as compared to smoking yet the impact of edibles on driving and associated blood THC has never been studied.

Methods: Participants drove a driving simulator before and after ingesting their preferred legally purchased cannabis edible. In a counterbalanced control session, participants did not consume any THC or cannabidiol (CBD). Blood was collected for measurement of THC and metabolites as well as CBD. Subjective experience was also assessed.

Results: Participants consumed edibles with, on average, 7.3 mg of THC, which is less than the maximum amount available in a single retail package in Ontario, providing an ecologically valid test of cannabis edibles. Compared to control, cannabis edibles produced a decrease in mean speed 2 h after consumption but not at 4 and 6 h. Under dual task conditions in which participants completed a secondary task while driving, changes in speed were not significant after the correction for multiple comparison. No changes in standard deviation of lateral position (SDLP; 'weaving'), maximum speed, standard deviation of speed or reaction time were found at any time point or under either standard or dual task conditions. Mean THC levels were significantly increased, relative to control, after consuming the edible but remained relatively low at approximately 2.8 ng/mL 2 h after consumption. Driving impairment was not correlated with blood THC. Subjective experience was altered for 7 h and participants were less willing/able to drive for up to 6 h, suggesting that the edible was intoxicating.

Interpretation: This is the first study of the impact of cannabis edibles on simulated driving. Edibles were intoxicating as revealed by the results of subjective assessments (VAS), and there was some impact on driving. Detection of driving impairment after the use of cannabis edibles may be difficult.

Cancer comes in second place on the list of causes of death worldwide. In 2018, the 5-year prevalence of breast cancer (BC), prostate cancer (PC), and colorectal cancer (CRC) were 30%, 12.3%, and 10.9%, respectively. Cannabinoids are chemicals derived from the Cannabis sativa plant; the most investigated cannabinoids are cannabinol, delta 9-tetrahydrocannabinol (Δ⁹-THC), and cannabidiol. In humans, the endogenous endocannabinoid system consists of endocannabinoids, cannabinoids receptors (CBs), and enzymes that degrade the endocannabinoids. In this review, we will review the most recent literature for evidence that discusses the role of cannabis in the treatment of the three types of neoplasms mentioned. Studies have proved that BC cells express CB receptors; many in-vivo studies showed that cannabinoids cause apoptosis and inhibit proliferation and migration. Also, researchers found that treating BC mice with THC and JWH-133 (CB2 receptor agonist) slowed the tumor growth. Regarding CRC, cannabidiol was found to decrease the viability of chemotherapy-resistant CRC cells and inhibit metastasis by antagonizing the G-protein-coupled receptor 55 (GPR55; a novel cannabinoid receptor) necessary for metastasis. Moreover, cannabidiol had anti-angiogenetic effects by reducing the expression of vascular endothelial growth factor (VEGF) in addition to anti-inflammatory effects. Finally, studies demonstrated that PC cells highly express CB1 and CB2 receptors and that cannabinoids are capable of inhibiting the release of exosomes and microvesicles related to cancer progression. Cannabinoids also have antiproliferative, anti-invasive, anti-fibroblastic, cell cycle arrest, and proapoptotic effects on PC cells.

Background: Cultivation of Cannabis and its use for medical purposes has existed for millennia on the African continent. The plant has also been widely consumed in the African continent since time immemorial. In particular, Lesotho has been largely growing Cannabis since approximately the 1550s and was illegally grown and unlawfully used for both medicinal and recreational purposes. It was only in 2017 when Lesotho started licensing Cannabis companies and regulating cultivation of Cannabis for medicinal purposes. However, the Lesotho Cannabis industry seems to have excluded the Small, Medium and Micro Enterprises (SMMEs) in the legalisation of Cannabis, the sector has the potential for small Cannabis enterprises in Lesotho.

Objective: This study attempts to examine challenges facing the evolving Cannabis sector in Lesotho as envisaged by Cannabis company managers with the aim of being proactive while addressing such challenges.

Methods: The qualitative descriptive method was employed using both primary and secondary data. For the selection of the three Cannabis managers exponential non-discriminative snowball sampling was adopted and interviews with the managers were recorded and transcribed verbatim. Thematic analysis was used to analyse the descriptive explanations of the Cannabis managers to determine the themes that were further consolidated into categories.

Results: The implementation and compliance with the laws in the Lesotho medicinal Cannabis sector has proved very challenging, with long timeframes for finalising regulatory frameworks and not being applied objectively. The industry does not provide opportunities for Small, Medium and Micro Enterprises (SMMEs) to venture into the Cannabis business.

Conclusion: In Lesotho, the Cannabis sector appears to be faced with many challenges emanating from the implementation and enforcement of Cannabis laws. The Lesotho Government should review its Cannabis laws and regulations with a view to benefiting SMMEs and legalising Cannabis production so as to serve both the domestic and international markets.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies with a median 5 year-survival rate of 12%. Cannabidiol (CBD) has been found to exhibit antineoplastic potential and may potentiate the anticancer effects of cytotoxic's such as gemcitabine. CBD therapy has been linked to de novo synthesis of ceramide. The sphingolipid ceramide is a potent tumour suppressor lipid with roles in apoptosis and autophagy. One of the key players involved is ceramide synthase, an enzyme with six isoforms (CerS1-CerS6), reported to have disease prognostic value. Quantitative real time PCR was used to determine mRNA expression levels of ceramide synthase isoforms, GRP78, ATF4 and CHOP. Western blotting was used to analyze protein expression of these markers and knockdown of CerS1 and GRP78 were applied via an siRNA and confirmed by the two mentioned methods. Mice with PDAC xenografts were injected via intraperitoneal method with drugs and tumours were analysed with flow cytometry and processed using H&E and IHC staining. siRNA knockdown of ceramide synthase 1 (CerS1) and analysis point to evidence of a putative CerS1 dependent pathway driven by CBD in activating endoplasmic reticulum (ER) stress target; GRP78. Upon CBD treatment, CerS1 was upregulated and downstream this led to the GRP78/ATF4/CHOP arm of the unfolded protein response (UPR) pathway being activated. In an in vivo model of PDAC in which CerS1 was not upregulated on IHC, there was no observed improvement in survival of animals, however a reduction in tumour growth was observed in combination chemotherapy and CBD group, indicating further investigations in vivo. These findings provide evidence of a potential ceramide induced cytotoxic mechanism of action of CBD in pancreatic ductal adenocarcinoma.

Since its discovery as one of the main components of cannabis and its affinity towards the cannabinoid receptor CB1, serving as a means to exert its psychoactivity, Δ⁹-tetrahydrocannabinol (Δ⁹-THC) has inspired medicinal chemists throughout history to create more potent derivatives. Initially, the goal was to synthesize chemical probes for investigating the molecular mechanisms behind the pharmacology of Δ⁹-THC and finding potential medical applications. The unintended consequence of this noble intent has been the proliferation of these compounds for recreational use. This review comprehensively covers the most exhaustive number of THC-like cannabinoids circulating on the recreational market. It provides information on the chemistry, synthesis, pharmacology, analytical assessment, and experiences related to the psychoactive effects reported by recreational users on online forums. Some of these compounds can be found in natural cannabis, albeit in trace amounts, while others are entirely artificial. Moreover, to circumvent legal issues, many manufacturers resort to semi-synthetic processes starting from legal products extracted from hemp, such as cannabidiol (CBD). Despite the aim to encompass all known THC-like molecules, new species emerge on the drug users' pipeline each month. Beyond posing a significantly high public health risk due to unpredictable and unknown side effects, scientific research consistently lags behind the rapidly evolving recreational market.