Cannabinoids, the endocannabinoid system, and pain: a review of preclinical studies

Pain, Journal Year: 2021, Volume and Issue: 162(1), P. S5 - S25

Published: March 15, 2021

This narrative review represents an output from the International Association for Study of Pain's global task force on use cannabis, cannabinoids, and cannabis-based medicines pain management, informed by our companion systematic meta-analysis preclinical studies in this area. Our aims are (1) to describe value studying cannabinoids endogenous cannabinoid (endocannabinoid) system modulators preclinical/animal models pain; (2) discuss both pain-related efficacy additional pain-relevant effects (adverse beneficial) endocannabinoid as they pertain animal pathological or injury-related persistent (3) identify important directions future research. In service these goals, provides overview pharmacology modulators, with specific relevance describes pharmacokinetics rodents humans; highlights differences discrepancies between clinical Preclinical (rodent) have advanced understanding underlying sites mechanisms action suppressing nociceptive signaling behaviors. We conclude that substantial evidence supports contention hold considerable promise analgesic drug development, although challenge translating knowledge into clinically useful is not be underestimated.

Language: Английский

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Lower-Risk Cannabis Use Guidelines (LRCUG) for reducing health harms from non-medical cannabis use: A comprehensive evidence and recommendations update

International Journal of Drug Policy, Journal Year: 2021, Volume and Issue: 99, P. 103381 - 103381

Published: Aug. 28, 2021

Cannabis use is common, especially among young people, and associated with risks for various health harms. Some jurisdictions have recently moved to legalization/regulation pursuing public goals. Evidence-based 'Lower Risk Use Guidelines' (LRCUG) recommendations were previously developed reduce modifiable risk factors of cannabis-related adverse outcomes; related evidence has evolved substantially since. We aimed review new scientific develop comprehensively up-to-date LRCUG, including their recommendations, on this basis. Targeted searches literature (since 2016) main outcomes by the user-individual conducted. Topical areas informed previous LRCUG content expanded upon current evidence. Searches preferentially focused systematic reviews, supplemented key individual studies. The results evidence-graded, topically organized narratively summarized; through an iterative expert consensus development process. A substantial body cannabis use-related harms identified varying quality. Twelve substantive recommendation clusters three precautionary statements developed. In general, suggests that individuals can if they delay onset until after adolescence, avoid high-potency (THC) products high-frequency/-intensity use, refrain from smoking-routes administration. While people are particularly vulnerable harms, other sub-groups (e.g., pregnant women, drivers, older adults, those co-morbidities) advised exercise particular caution risks. Legal/regulated should be used where possible. result in outcomes, mostly higher-risk use. Reducing help offer one targeted intervention component within a comprehensive approach They require effective audience-tailoring dissemination, regular updating as become available, evaluated impact.

Language: Английский

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Assessment of Orally Administered Δ9-Tetrahydrocannabinol When Coadministered With Cannabidiol on Δ9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics in Healthy Adults: A Randomized Clinical Trial

JAMA Network Open, Journal Year: 2023, Volume and Issue: 6(2), P. e2254752 - e2254752

Published: Feb. 13, 2023

Importance Controlled clinical laboratory studies have shown that cannabidiol (CBD) can sometimes attenuate or exacerbate the effects of Δ 9-tetrahydrocannabinol ( 9-THC). No evaluated differences in pharmacokinetics (PK) 9-THC and pharmacodynamics (PD) between orally administered cannabis extracts vary with respect to CBD concentrations. Objective To compare PK PD 9-THC-dominant CBD-dominant contained same dose (20 mg). Design, Setting, Participants This randomized trial was a within-participant, double-blind, crossover study conducted from January 2021 March 2022 at Johns Hopkins University Behavioral Pharmacology Research Unit, Baltimore, MD. Eighteen healthy adults completed 3 outpatient experimental test sessions were each separated by least 1 week. Interventions Brownies containing (1) no extract (ie, placebo); (2) mg CBD); (3) + 640 CBD) participants 30 minutes prior administering cytochrome P450 (CYP) probe drug cocktail, which consisted 100 caffeine, 20 omeprazole, 25 losartan, dextromethorphan, 2 midazolam. Main Outcomes Measures Change-from-baseline plasma concentrations for metabolites scores subjective effects, cognitive psychomotor performance, vital signs. The area under vs concentration time curve (AUC) maximum (C max ) determined. Results participant cohort 18 included 11 males (61.1%) 7 females (38.9%) mean (SD) age (7) years who had not used days initiation (mean [SD] day since last use, 86 [66] days). CYP cocktail placebo brownie did affect any assessments. Relative 9-THC, produced higher C 11-OH- 9-THC-COOH. increased self-reported anxiety, sedation, memory difficulty, heart rate, more pronounced impairment performance compared both Δ9-THC placebo. Conclusions Relevance In this oral CBD, stronger adverse elicited dose, contradicts common claims attenuates 9-THC. inhibition metabolism is likely mechanism observed. An improved understanding cannabinoid-cannabinoid cannabinoid-drug interactions are needed inform regulatory decision-making regarding therapeutic nontherapeutic use products. Trial Registration clinicaltrials.gov Identifier: NCT04201197

Language: Английский

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Pharmacokinetics and central accumulation of delta-9-tetrahydrocannabinol (THC) and its bioactive metabolites are influenced by route of administration and sex in rats

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: Dec. 14, 2021

Abstract Up to a third of North Americans report using cannabis in the prior month, most commonly through inhalation. Animal models that reflect human consumption are critical study impact on brain and behaviour. Most animal studies date utilize injection delta-9-tetrahydrocannabinol (THC; primary psychoactive component cannabis). THC injections produce markedly different physiological behavioural effects than inhalation, likely due distinctive pharmacokinetics. The current directly examined if administration route (injection versus inhalation) alters metabolism central accumulation metabolites over time. Adult male female Sprague–Dawley rats received either an intraperitoneal or 15-min session inhaled exposure THC. Blood brains were collected at 15, 30, 60, 90 240-min post-exposure for analysis metabolites. Despite achieving comparable peak blood concentrations both groups, our results indicate higher initial concentration following whereas resulted dramatically 11-OH-THC concentration, potent metabolite, increased Our provide evidence pharmacokinetic profiles inhalation injection. Accordingly, should be considered during data interpretation, translational work strongly consider models.

Language: Английский

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Endocannabinoids, cannabinoids and the regulation of anxiety

Neuropharmacology, Journal Year: 2021, Volume and Issue: 195, P. 108626 - 108626

Published: June 8, 2021

Language: Английский

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Assessment of cognitive and psychomotor impairment, subjective effects, and blood THC concentrations following acute administration of oral and vaporized cannabis

Journal of Psychopharmacology, Journal Year: 2021, Volume and Issue: 35(7), P. 786 - 803

Published: May 28, 2021

Background: Cannabis legalization is expanding, but there are no established methods for detecting cannabis impairment. Aim: Characterize the acute impairing effects of oral and vaporized using various performance tests. Methods: Participants ( N = 20, 10 men/10 women) who were infrequent users ingested brownies (0, 10, 25 mg Δ-9-tetrahydrocannabinol, THC) inhaled 5, 20 in six double-blind outpatient sessions. Cognitive/psychomotor impairment was assessed with a battery computerized tasks sensitive to effects, novel test (the DRiving Under Influence Drugs, DRUID ® ), field sobriety Blood THC concentrations subjective drug evaluated. Results: Low oral/vaporized doses did not impair cognitive/psychomotor relative placebo produced positive effects. High impaired increased negative The most impairment, as it detected significant differences between active within both routes administration. Women displayed more on than men at high dose only. Field tests showed little sensitivity cannabis-induced far lower after ingestion versus inhalation. After inhalation, blood typically returned baseline well before pharmacodynamic subsided. Conclusions: Standard approaches identifying due exposure (i.e. tests) have severe limitations. There need identify biomarkers and/or behavioral like that can reliably accurately detect roadside workplace.

Language: Английский

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The why behind the high: determinants of neurocognition during acute cannabis exposure

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(7), P. 439 - 454

Published: May 27, 2021

Language: Английский

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Clinical and cognitive improvement following full-spectrum, high-cannabidiol treatment for anxiety: open-label data from a two-stage, phase 2 clinical trial

Communications Medicine, Journal Year: 2022, Volume and Issue: 2(1)

Published: Nov. 2, 2022

Abstract Background Evidence suggests cannabidiol (CBD) has anxiolytic properties, indicating potential for novel treatment strategies. However, few clinical trials of CBD-based products have been conducted, and none thus far examined the impact these on cognition. Methods For open-label stage trial NCT02548559, autoregressive linear modeling assessed efficacy tolerability four-weeks 1 mL t.i.d. with a full-spectrum, high-CBD sublingual solution (9.97 mg/mL CBD, 0.23 Δ−9-tetrahydrocannabinol) in 14 outpatients moderate-to-severe anxiety, defined as ≥16 Beck Anxiety Inventory (BAI) or ≥11 Overall Severity Impairment Scale (OASIS). Results Findings suggest significant improvement primary outcomes measuring anxiety secondary assessing mood, sleep, quality life, cognition (specifically executive function) following treatment. is significantly reduced at week 4 relative to baseline (BAI: 95% CI = [−21.03, −11.40], p < 0.001, OASIS: [−9.79, −6.07], 0.001). Clinically response (≥15% symptom reduction) achieved maintained early most patients (BAI 78.6%, OASIS 92.7%); cumulative frequency responders reached 100% by 3. The study drug well-tolerated, high adherence/patient retention no reported intoxication serious adverse events. Minor side effects, including sleepiness/fatigue, increased energy, dry mouth are infrequently endorsed. Conclusions provide preliminary evidence supporting product anxiety. Patients quickly achieve maintain reduction effects. A definitive assessment this symptoms will be ascertained ongoing double-blind, placebo-controlled stage.

Language: Английский

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Impacts of recreational cannabis legalization on use and harms: A narrative review of sex/gender differences

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: March 10, 2023

Legalization of cannabis use for non-medical (recreational) purposes is changing the global landscape. As attitudes toward become more positive and prevalence increases in complex ways, concerns emerge about potential increased cannabis-attributable harms. Understanding who, why, when this likely increase harms thus an important public health priority. Both sex gender contribute to variability use, effects, sex/gender considerations are evaluating impacts legalization. The goal narrative review broadly discuss differences whether there legalization, why these might exist. One our strongest conclusions that men have always been than women, yet gap has narrowed over time, be partly due existing evidence suggests also legalization on such as cannabis-involved motor vehicle collisions hospitalizations, though results variable. body literature reviewed focused almost exclusively samples cisgender research participants, future should encourage inclusion transgender gender-diverse participants. More consideration sex- gender-based analysis long-term a clear

Language: Английский

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The Complex Relationship Between Cannabis Use and Mental Health: Considering the Influence of Cannabis Use Patterns and Individual Factors

CNS Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Language: Английский

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