Cannabis and Cannabinoid Research最新文献

Objective: Cannabis has been touted for a host of pharmacological and therapeutic effects and users commonly report reduced symptoms of physical and mental health conditions, including anxiety, depression, and chronic pain. While there is existing empirical evidence supporting these effects of cannabis use, little is known about the extent to which these effects result from pharmacological versus expectancy factors. We evaluated the associations between participants' cannabis expectancies and their acute self-reported reactions after using legal market forms of cannabis with varying levels of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in three domains: anxiety, depression, and pain. Methods: Fifty-five flower and 101 edible cannabis users were randomly assigned and asked to purchase at a local dispensary one of three products containing varying levels of CBD and THC. Participants completed a baseline assessment where they reported expectancies about general health effects of cannabis use and an experimental mobile laboratory assessment where they administered their assigned products. Edible users also reported their domain-specific expectancies about cannabis use in improving anxiety, depression, and pain. Following administration, participants completed acute indicators of anxiety, depression, and pain operationalized through subjective acute tension, elation, and a single-item measure of pain. Results: Among flower users, more positive expectancies for cannabis to improve general health were correlated with greater reductions in tension at acute post-use. This finding was replicated among edible users. Unlike flower users, more positive expectancies for cannabis to improve general health were also correlated with greater increases in elation and greater reductions in pain among edible users. More positive expectancies for cannabis to improve depression and pain were also correlated with greater increases in elation and greater reductions in pain, respectively, among edible users. Conclusions: Cannabis users' expectancies significantly impacted some of the acute subjective effects of legal market cannabis products. Among both flower and edible users, consistent, significant expectancy effects were found. Results were consistent with prior findings and demonstrate the need to measure and control pre-existing expectancies in future research that involves cannabis administration. Clinical trial registration number: NCT03522103.

Introduction: Cannabichromene (CBC) is a minor constituent of cannabis that is a selective cannabinoid CB2 receptor agonist and activator of TRPA1. To date, it has not been shown whether (-)-CBC, (+)-CBC, or both can mediate these effects. In this study, we investigate the activity of the CBC enantiomers at CB1, CB2, and Transient receptor potential ankyrin 1 (TRPA1) receptors in vitro. Materials and Methods: CBC enantiomers were purified from synthetic CBC by chiral chromatography, and their optical activity was confirmed by spectroscopy. Human CB1 and CB2 receptor activity was measured using a fluorescent assay of membrane potential in stably transfected AtT20 cells. TRPA1 activation was measured using a fluorescent assay of intracellular calcium in stably transfected HEK293 cells. Results: The (-)-CBC activated CB2 with an EC₅₀ of 1.5 µM, to a maximum of 60% of (-)CP55940. (+)-CBC did not activate CB2 at concentrations up to 30 µM. Only 30 µM (-)-CBC produced detectable activation of CB1, (+)-CBC was inactive. Both (-)-CBC and (+)-CBC activated TRPA1; at 30 µM (-)-CBC produced an activation 50% of that of the reference agonist cinnamaldehyde (300 µM), 30 µM (+)-CBC activated TRPA1 to 38% of the cinnamaldehyde maximum. Discussion: It is unclear whether (-)-CBC is the sole or even the predominant enantiomer of CBC enzymatically synthesized in cannabis. This study shows that (-)-CBC is the active isomer at CB2 receptors, while both isomers activate TRPA1. The results suggest that medicinal preparations of CBC that target cannabinoid receptors would be most effective when (-)-CBC is the dominant isomer.

Tetrahydrocannabivarin (THCV) is a phytocannabinoid that is becoming popular across the North American cannabis market. THCV has been reported to reduce blood sugar and act as an appetite suppressant in several independent pre-clinical studies, which has earned it the popular nickname of "diet weed," despite few human studies of these effects. Additionally, THCV is usually and incorrectly categorized as an intoxicating analogue of tetrahydrocannabinol (THC), which causes confusion among both consumers and regulators. In this article, we examine what is known pre-clinically and clinically about THCV, as well as highlight mechanisms of action, in order to clarify the scientific differences between THCV and THC. THCV, although structurally similar to THC, has distinct pharmacological activity and physiological effects at the doses currently reported in the literature. We highlight areas of opportunity for further THCV research in order to determine the full and appropriate potential for unique health, wellness, and therapeutic applications of this compound.

Introduction: Post-surgical pain arises following a clinical operation, often persisting throughout recovery. While current treatments reduce pain, repeated use increases the probability of adverse events. monoacylglycerol lipase (MAGL) inhibition has previously been shown to produce analgesia, either through CB₁ or CB₂ mechanisms, dependent on the underlying pain phenotype. Thus, this study investigated the analgesic potential of inhibiting MAGL, alone and in combination with the analgesic non-steroidal anti-inflammatory drug (NSAID) diclofenac sodium in a model of post-surgical pain. Methods: Male and female C57BL/6J mice were subjected to hindpaw incision (HPI) surgery. Mechanical allodynia, climbing, grip strength, and thermal preference were measured 24 h following HPI. The dose-dependent anti-allodynic effects of the MAGL inhibitors (irreversible MAGL inhibitor [JZL184] and selective MAGL inhibitor [MJN110]) and the NSAID diclofenac, as well as the additive potential of combined MAGL and cyclooxygenase (COX) inhibition, were assessed. Selective antagonists of CB₁ and CB₂ receptors were used to challenge the cannabinoid-receptor mechanism of JZL184. Similarly, the anti-allodynic effects of the CB₂-selective agonist (LY2828360) were tested. JZL184 was administered repeatedly to determine tolerance. Finally, hindpaw cytokines were quantified via multiplex ELISA 24 h after HPI surgery. Results: Approximately 24 h post-surgery, the MAGL inhibitors JZL184 (≥4 mg/kg) or MJN110 (≥5 mg/kg), as well as the NSAID diclofenac sodium (≥16.67 mg/kg), attenuated HPI-induced mechanical allodynia, as assessed with von Frey filaments. The anti-allodynic effects of JZL184 (40 mg/kg) were blocked by pre-treatment of the CB₂ antagonist SR144528 (3 mg/kg) but not the CB₁-selective antagonist rimonabant (SR141716A; 3 mg/kg), suggesting a CB₂-mediated mechanism of anti-allodynia via MAGL inhibition. Similarly, LY2828360 (3 mg/kg) reduced HPI-induced allodynia. Moreover, when administered repeatedly, the anti-allodynic effects of JZL184 (8 mg/kg) persisted and did not undergo tolerance. A separate cohort was administered a sub-analgesic dose of JZL184 (1 mg/kg), diclofenac sodium (1.85 mg/kg), or both compounds concurrently. This subthreshold JZL184 and diclofenac sodium combination attenuated HPI-induced allodynia, suggesting an additive drug interaction. Finally, HPI per se increased pro-inflammatory cytokine levels, which were unaltered by MAGL inhibition despite the anti-allodynia assessed behaviorally. Conclusion: These data support simultaneously targeting endocannabinoids and COX enzymes as a potential post-operative pain management approach.

Background: Although research suggests that early-life adversity (ELA) and cannabis use are linked, researchers have not established factors that mediate or modify this relationship. Identifying such factors could help in developing targeted interventions. We explored chronic pain as a potential mediator or moderator of this relationship. Methods: Using an online study, we collected cross-sectional data about ELA, cannabis use, and chronic pain to test whether ELA (adverse childhood experiences total score) is associated with cannabis use, and to examine pain as a potential mediator or moderator. Cannabis use was examined two ways: times used per day, and categorized as non-, some, or regular use. Chronic pain was measured as present/absent and as the number of painful body locations (0-8). Analyses used linear and multinomial regression. Results: ELA, chronic pain, and cannabis use were common among respondents. ELA was strongly associated with both measures of cannabis use. The number of painful body locations modestly mediated the association of ELA with cannabis use, reducing the magnitude of regression coefficients by about 1/7. The number of painful body locations modified the association between ELA and cannabis use (p≤0.006), while chronic pain presence/absence (a less-informative measure) had only a nonsignificant modification effect (p≥0.10). When either ELA or pain was high, the other was not associated with cannabis use; when either ELA or pain was low, more painful locations or higher ELA (respectively) was associated with more intense cannabis use. Conclusion: These exploratory findings suggest the importance of ELA and chronic pain as factors contributing to cannabis use, and of accounting for these factors in developing treatment and prevention strategies addressing cannabis use.

Background and Aims: This investigation examined the association of pancreatitis and pancreatitis-related pain with serum levels of two endocannabinoid molecules such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and two paracannabinoid molecules such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Methods: A case-control study was conducted within the Prospective Evaluation of Chronic Pancreatitis for Epidemiological and Translational Studies, including participants with no pancreas disease (N = 56), chronic abdominal pain of suspected pancreatic origin or indeterminate chronic pancreatitis (CP) (N = 22), acute pancreatitis (N = 33), recurrent acute pancreatitis (N = 57), and definite CP (N = 63). Results: Circulating AEA concentrations were higher in women than in men (p = 0.0499), and PEA concentrations were higher in obese participants than those who were underweight/normal or overweight (p = 0.003). Asymptomatic controls with no pancreatic disease had significantly (p = 0.03) lower concentrations of AEA compared with all disease groups combined. The highest concentrations of AEA were observed in participants with acute pancreatitis, followed by those with recurrent acute pancreatitis, chronic abdominal pain/indeterminant CP, and definite CP. Participants with pancreatitis reporting abdominal pain in the past year had significantly (p = 0.04) higher concentrations of AEA compared with asymptomatic controls. Levels of 2-AG were significantly lower (p = 0.02) among participants reporting abdominal pain in the past week, and pain intensity was inversely associated with concentrations of 2-AG and OEA. Conclusions: Endocannabinoid levels may be associated with stage of pancreatitis, perhaps through activation of the CB1 receptor. Validation of our findings would support the investigation of novel therapeutics, including cannabinoid receptor-1 antagonists, in this patient population.

Introduction: Studies show that acute cannabis use significantly increases heart rate (HR) and mildly raises blood pressure in the minutes following smoked or inhaled use of cannabis. However, less is known about how the THC concentration of the product or an individual's frequency of use (i.e., tolerance) may affect the magnitude of the change in HR. It is also relatively unexamined how the physical effects of increased HR after acute cannabis use relate to self-reported drug effects or blood THC levels. Aims: To describe the relationship between THC concentration of product used, self-reported subjective intoxication, THC blood levels, and frequency of cannabis use with the change in HR after acute cannabis use. Materials and Methods: Participants (n = 140) were given 15 min to smoke self-supplied cannabis ad libitum, HR was measured at baseline and an average of 2 min post-cannabis smoking. The ARCI-Marijuana scale and Visual Analog Scales (VAS) were administered, and blood samples were taken at both time points. Participants were asked about their frequency of use. Information about the product used was recorded from the package. Linear regression was used to analyze the relationship between changes in HR (post-pre cannabis use) and post-cannabis use HR, blood THC concentration, THC product concentration, frequency of use, and self-reported drug effect. Results: There was a significantly higher HR among those who smoked cannabis compared to the controls (p < 0.001), which did not significantly differ by frequency of use (p = 0.18). Higher concentration THC (extract) products did not produce a significantly different HR than lower concentration (flower) products (p = 0.096). VAS score was associated with an increase in HR (p < 0.05). Overall, blood THC levels were not significantly related to the change in HR (p = 0.69); however, when probed, there was a slight positive association among the occasional use group only. Discussion: Cardiovascular effects of cannabis consumption may not be as subject to tolerance with daily cannabis use and do not directly increase with THC concentration of the product. This is a departure from other effects (i.e., cognitive, subjective drug effects) where tolerance is well established. These findings also suggest that, at least among those with daily use, higher concentration THC products (>60%) do not necessarily produce cardiovascular physiological effects that are significantly more robust than lower concentration (<20%) products.

Introduction: Cannabis vaporization is useful for individuals requiring fast-acting method of cannabis administration and for individuals using smoked cannabis as a harm reduction tool. There is a need for guidance on how to assess if a patient is a vaporization candidate and how to safely initiate and monitor cannabis vaporization. Methods: An overview of safe cannabis vaporization, including practical guidance and tactics to promote the lowest-risk use, is provided. This review was developed through a combination of expert clinical opinion and reviewing the available literature. Results: Dried cannabis vaporizers and metered-dose inhalers are recommended to be used over other vaporization devices. Assessing the benefit versus risks of vaporized cannabis and providing guidance for choosing a vaporization device, choosing a cannabis chemovar, and employing a mindful vaping technique are important steps in the safe utilization of vaporized cannabis. Dosing optimization and monitoring to limit adverse events and improve symptom control are essential. Discussion: The utilization of cannabis vaporization presents an important opportunity for clinicians and other health professionals to help facilitate safer cannabis administration and reduce the prevalence of smoked cannabis.

Purpose: Inflammatory bowel disease (IBD) has two main variants, ulcerative colitis (UC) and Crohn's disease (CD), which are characterized by a cycle of remission and relapse. The aim of this scoping review is to understand the landscape of unprescribed and prescribed cannabis use among patients with IBD and investigate objective clinical benefits. Methodology: A literature search was performed across Medline, Embase via Ovid, Scopus, and Cochrane Library databases. We included 40 studies (14 abstracts/letters, 7 randomized controlled trials [RCTs], 6 cohort studies [2 case-matched], 10 cross-sectional surveys, and 3 meta-analyses) in the review. Results: Between 11% and 17.6% of surveyed patients used cannabis for symptom control with a lifetime prevalence of 39.8-78.2%. Patients reported reduced abdominal pain, emotional distress, stool frequency, and anorexia. There was a higher rate of depression, tobacco, and alcohol use among patients with IBD who used cannabis. Individual studies showed patients who were prescribed cannabis were more likely to have had surgery for IBD (14.5% vs. 4.7%, p = 0.0008), require future abdominal surgery (odds ratio = 5.03), report a lower quality of life (p = 0.0001), currently be on corticosteroids (18.1% vs. 10.4%, p = 0.04) and opioids (27.7% vs. 6.4%, p = 0.0001). RCTs of cannabinoids reported mild reductions in disease activity and variable endoscopic inflammation improvement. Conclusions: Patients who use cannabis for IBD are a cohort with refractory disease and lower quality of life who report improvements in symptom management. However, the ability to reduce underlying disease activity appears very modest. Further trials using refined cannabinoid formulations may define a use in IBD.