Expert Rev Neurother. 2023 Apr 6:1-11. doi: 10.1080/14737175.2023.2195551. Online ahead of print.

ABSTRACT

BACKGROUND: The following study evaluated the clinical outcomes of patients enrolled in the UK Medical Cannabis Registry, who were treated with inhaled dried flower (Adven® EMT2, Curaleaf International, Guernsey), and sublingual/oral medium-chain triglyceride-based oils (Adven, Curaleaf International, Guernsey) for chronic pain.

METHODS: In this cohort study, the primary outcomes were changes in validated patient reported outcome measures (PROMs) at 1, 3, and 6 months compared to baseline, and adverse event analysis. Statistical significance was defined as p < 0.050.

RESULTS: Three hundred and forty-eight (45.7%), 36 (4.7%), and 377 (49.5%) patients were treated with oils, dried flower, or both, respectively. Patients treated with oils or combination therapy recorded improvements within health-related quality of life, pain, and sleep-specific PROMs at 1, 3, and 6 months (p < 0.050). Patients treated with combination therapy recorded improvements in anxiety-specific PROMs at 1, 3, and 6 months (p < 0.050). 1,273 (167.3%) adverse events were recorded, with previously cannabis naïve users, ex-cannabis users, and females more likely to experience adverse events (p < 0.050).

CONCLUSIONS: This study observed an association between initiation of CBMP treatment and improved outcomes for chronic pain patients. Prior cannabis use and gender were associated with adverse event incidence. Placebo-controlled trials are still necessary to establish the efficacy and safety of CBMPs for chronic pain.

PMID:37021592 | DOI:10.1080/14737175.2023.2195551

Cannabis Cannabinoid Res. 2023 Apr 13. doi: 10.1089/can.2022.0254. Online ahead of print.

ABSTRACT

Background: Spasticity continues to be a very prevalent, highly invalidating, and difficult-to-manage symptom in patients with multiple sclerosis (MS). The aim of this systematic review is to evaluate the effectiveness of the use of cannabis and cannabinoids in these patients, evaluating its use as an additional therapy. Methods: We performed a systematic review of the literature searching in the major scientific databases (PubMed, Scopus, EMBASE, WOS, and Cochrane Library) for articles from January 2017 to May 2022 containing information about the effectiveness of cannabis and cannabinoids in patients with insufficient response to first-line oral antispastic treatment. Results: A total of five medium high-quality articles were selected to be part of the study and all evaluated the effectiveness of the tetrahydrocannabinol (THC) and cannabidiol (CBD) spray. The effectiveness of this drug and the significant improvements are produced on the patient-related spasticity assessment scales, obtaining improvement up to 45%; and on quality of life, producing a decrease in the appearance of symptoms related to spasticity, as well as an increase in the development of basic activities of daily living. The average dose is 5-7 sprays/day. The discontinuation rate for these treatments is around 40% due to lack of effectiveness and adverse events. All reported adverse effects are mild to moderate in severity and their incidence is ∼17%, although this figure tends to decrease with drug use. Conclusions: Adding the THC:CBD sprays have been shown to be more effective in treating MS spasticity than optimizing the dose of first-line antispastic drugs in selected responders patients. The safety and tolerability profiles remain in line with those obtained in other trials. More patients would benefit from treatment if the initial response search period was extended.

PMID:37057959 | DOI:10.1089/can.2022.0254

Front Psychiatry. 2023 Mar 30;14:1155984. doi: 10.3389/fpsyt.2023.1155984. eCollection 2023.

ABSTRACT

INTRODUCTION: Opioid use disorder (OUD) continues to be a significant public health concern. Medications for OUD (MOUD) such as buprenorphine reduce overdose mortality, but relapses occur often, leading to adverse outcomes. Preliminary data suggest that cannabidiol (CBD) may be a potential adjunctive treatment to MOUD by attenuating cue-reactivity. This pilot study sought to evaluate the impact of a single dose of CBD on reward- and stress-related neurocognitive processes implicated in relapse among those with OUD.

METHODS: The study was a pilot, double-blind, placebo-controlled, randomized cross-over trial aimed at assessing the effects of a single dose of CBD (Epidiolex®) 600 mg or matching placebo administered to participants with OUD receiving either buprenorphine or methadone. Vital signs, mood states, pain, opioid withdrawal, cue-induced craving, attentional bias, decision-making, delayed discount, distress tolerance, and stress-reactivity were examined at each testing session on two separate testing days at least 1 week apart.

RESULTS: Ten participants completed all study procedures. Receipt of CBD was associated with a significant decrease in cue-induced craving (0.2 vs. 1.3, p = 0.040), as well as reduced attentional bias toward drug-related cues as measured by the visual probe task (-80.4 vs. 100.3, p = 0.041). No differences were found among all the other outcomes examined.

DISCUSSION: CBD may have promise as an adjunct to MOUD treatment by attenuating the brain response to drug-related cues, which, in turn, may reduce the risk of relapse and overdoses. Further research is warranted to evaluate the potential for CBD as an adjunctive therapy for individuals in treatment for OUD.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04982029.

PMID:37065899 | PMC:PMC10098189 | DOI:10.3389/fpsyt.2023.1155984

Int J Environ Res Public Health. 2023 Feb 24;20(5):4087. doi: 10.3390/ijerph20054087.

ABSTRACT

Substance-use disorders are pervasive, comorbid with a plethora of disease and possess limited treatment options. Medicinal cannabinoids have been proposed as a novel potential treatment based on preclinical/animal trials. The objective of this study was to examine the efficacy and safety of potential therapeutics targeting the endocannabinoid system in the treatment of substance-use disorders. We performed a scoping review using a systematic approach of systematic reviews, narrative reviews, and randomised control trials that utilised cannabinoids as treatment for substance-use disorders. For this scoping review we used the PRISMA guidelines, a framework for systematic reviews and meta-analyses, to inform our methodology. We conducted a manual search of Medline, Embase, and Scopus databases in July 2022. Of the 253 results returned by the databases, 25 studies including reviews were identified as relevant, from which 29 randomised controlled trials were derived and analysed via a primary study decomposition. This review captured a small volume of highly heterogenous primary literature investing the therapeutic effect of cannabinoids for substance-use disorders. The most promising findings appeared to be for cannabis-use disorder. Cannabidiol appeared to be the cannabinoid showing the most promise for the treatment of multiple-substance-use disorders.

PMID:36901098 | DOI:10.3390/ijerph20054087

Curr Neuropharmacol. 2023 Mar 22. doi: 10.2174/1570159X21666230322143401. Online ahead of print.

ABSTRACT

BACKGROUND: Compelling evidence from preclinical and clinical studies supports the therapeutic role of cannabidiol (CBD) in several medical disorders. We reviewed the scientific evidence on CBD-related toxicity and adverse events (AEs) in 2019, at the beginning of the spike in clinical studies involving CBD. However, CBD safety remained uncertain.

OBJECTIVE: With the benefit of hindsight, we aimed to provide an update on CBD-related toxicity and AEs in humans.

METHODS: A systematic literature search was conducted following PRISMA guidelines. PubMed, Cochrane, and Embase were accessed in October 2022 to identify clinical studies mentioning CBD-related toxicity/AEs from February 2019 to September 2022. Study design, population characteristics, CBD doses, treatment duration, co-medications, and AEs were compiled.

RESULTS: A total of 51 reports were included. Most studies investigated CBD efficacy and safety in neurological conditions, such as treatment-resistant epilepsies, although a growing number of studies are focusing on specific psychopathological conditions, such as substance use disorders, chronic psychosis, and anxiety. Most studies report mild or moderate severity of AEs. The most common AEs are diarrhea, somnolence, sedation, and upper respiratory disturbances. Few serious AEs have been reported, especially when CBD is co-administered with other classes of drugs, such as clobazam and valproate.

CONCLUSIONS: Clinical data suggest that CBD is well tolerated and associated with few serious AEs at therapeutic doses both in children and adults. However, interactions with other medications should be monitored.

PMID:36946485 | DOI:10.2174/1570159X21666230322143401

Psychiatry Res. 2023 Feb 28;323:115135. doi: 10.1016/j.psychres.2023.115135. Online ahead of print.

ABSTRACT

Preliminary data suggest that cannabis-based medicines might be a promising new treatment for patients with Tourette syndrome (TS)/chronic tic disorders (CTD) resulting in an improvement of tics, comorbidities, and quality of life. This randomized, multicenter, placebo-controlled, phase IIIb study aimed to examine efficacy and safety of the cannabis extract nabiximols in adults with TS/CTD (n = 97, randomized 2:1 to nabiximols:placebo). The primary efficacy endpoint was defined as a tic reduction of ≥ 25% according to the Total Tic Score of the Yale Global Tic Severity Scale after 13 weeks of treatment. Although a much larger number of patients in the nabiximols compared to the placebo group (14/64 (21·9%) vs. 3/33 (9·1%)) met the responder criterion, superiority of nabiximols could formally not be demonstrated. In secondary analyses, substantial trends for improvements of tics, depression, and quality of life were observed. Additionally exploratory subgroup analyses revealed an improvement of tics in particular in males, patients with more severe tics, and patients with comorbid attention deficit/hyperactivity disorder suggesting that these subgroups may benefit better from treatment with cannabis-based medication. There were no relevant safety issues. Our data further support the role of cannabinoids in the treatment of patients with chronic tic disorders.

PMID:36878177 | DOI:10.1016/j.psychres.2023.115135

Am J Hosp Palliat Care. 2023 Feb 15:10499091231158388. doi: 10.1177/10499091231158388. Online ahead of print.

ABSTRACT

Objective: Chronic pain is a major problem for patients with Charcot-Marie-Tooth (CMT) disease. This exploratory study examined patient reported efficacy of medical cannabis for pain management in this population. Methods: Participants (N = 56; 71.4% female; Age = 48.9, SD = 14.6; 48.5% CMT1) were recruited though the Hereditary Neuropathy Foundation. The online survey contained 52 multiple choice questions about demographics, medical cannabis use, symptomology, efficacy, and adverse effects. Results: Nearly all (90.9%) of respondents reported experiencing pain, including all (100%) females and 72.7% of males (chi-square P < .05) with 91.7% of respondents indicating cannabis provided at least 50% pain relief. The most frequent response was an 80% reduction in pain. Moreover, 80.0% of respondents reported using less opiates, 69% noted using less sleep medication, and 50.0% reported using less anxiety/antidepressant medications. Negative side effects were noted by 23.5% of respondents. However, almost all (91.7%) of that subgroup did not have plans to stop consuming cannabis. One-third (33.9%) possessed a medical cannabis certificate. Patient perceptions of their physicians' attitudes regarding patient medical cannabis use greatly impacted whether respondents informed their providers of their usage. Conclusion: The vast majority of patients with CMT reported that cannabis was effective to manage pain symptoms. These data support the need for prospective, randomized, controlled trials using standardized dosing protocols to further delineate and optimize the potential use of cannabis to treat pain related to CMT.

PMID:36793224 | DOI:10.1177/10499091231158388

PLoS One. 2023 Jan 30;18(1):e0267420. doi: 10.1371/journal.pone.0267420. eCollection 2023.

ABSTRACT

OBJECTIVES: To assess the benefits and harms of cannabinoids in participants with pain.

DESIGN: Systematic review of randomised clinical trials with meta-analysis, Trial Sequential Analysis, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

DATA SOURCES: The Cochrane Library, MEDLINE, Embase, Science Citation Index, and BIOSIS.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Published and unpublished randomised clinical trials comparing cannabinoids versus placebo in participants with any type of pain.

MAIN OUTCOME MEASURES: All-cause mortality, pain, adverse events, quality of life, cannabinoid dependence, psychosis, and quality of sleep.

RESULTS: We included 65 randomised placebo-controlled clinical trials enrolling 7017 participants. Fifty-nine of the trials and all outcome results were at high risk of bias. Meta-analysis and Trial Sequential Analysis showed no evidence of a difference between cannabinoids versus placebo on all-cause mortality (RR 1.20; 98% CI 0.85 to 1.67; P = 0.22). Meta-analyses and Trial Sequential Analysis showed that cannabinoids neither reduced acute pain (mean difference numerical rating scale (NRS) 0.52; 98% CI -0.40 to 1.43; P = 0.19) or cancer pain (mean difference NRS -0.13; 98% CI -0.33 to 0.06; P = 0.1) nor improved quality of life (mean difference -1.38; 98% CI -11.81 to 9.04; P = 0.33). Meta-analyses and Trial Sequential Analysis showed that cannabinoids reduced chronic pain (mean difference NRS -0.43; 98% CI -0.72 to -0.15; P = 0.0004) and improved quality of sleep (mean difference -0.42; 95% CI -0.65 to -0.20; P = 0.0003). However, both effect sizes were below our predefined minimal important differences. Meta-analysis and Trial Sequential Analysis indicated that cannabinoids increased the risk of non-serious adverse events (RR 1.20; 95% CI 1.15 to 1.25; P < 0.001) but not serious adverse events (RR 1.18; 98% CI 0.95 to 1.45; P = 0.07). None of the included trials reported on cannabinoid dependence or psychosis.

CONCLUSIONS: Cannabinoids reduced chronic pain and improved quality of sleep, but the effect sizes are of questionable importance. Cannabinoids had no effects on acute pain or cancer pain and increased the risks of non-serious adverse events. The harmful effects of cannabinoids for pain seem to outweigh the potential benefits.

PMID:36716312 | DOI:10.1371/journal.pone.0267420

BMC Complement Med Ther. 2023 Feb 20;23(1):57. doi: 10.1186/s12906-023-03886-0.

ABSTRACT

BACKGROUND: Although topical steroids constitute the first-line therapy for recurrent aphthous ulcers (RAUs), their long-term use often leads to candidiasis. Although cannabidiol (CBD) can be an alternative for pharmacologically managing RAUs due to its analgesic and anti-inflammatory in vivo effects, there is a lack of clinical and safety trials concerning its use. The aim of this study was to evaluate the clinical safety and efficacy of topical 0.1% CBD for managing RAU.

METHODS: A CBD patch test was performed on 100 healthy subjects. CBD was applied on the normal oral mucosa of 50 healthy subjects 3 times/day for 7 days. Oral examination, vital signs, and blood tests were performed pre- and post-CBD use. Another 69 RAU subjects randomly received one of three topical interventions: 0.1% CBD, 0.1% triamcinolone acetonide (TA), or placebo. These were applied on the ulcers 3 times/day for 7 days. The ulcer and erythematous size were measured on day 0, 2, 5, and 7. Pain ratings were recorded daily. The subjects rated their satisfaction with the intervention and completed a quality-of-life questionnaire (OHIP-14).

RESULTS: None of the subjects exhibited allergic reactions or side effects. Their vital signs and blood parameters were stable before and after the 7-day CBD intervention. CBD and TA significantly reduced ulcer size more than placebo at all time points. The erythematous size reduction was higher in the CBD intervention than the placebo on day 2, while TA reduced the erythematous size at all time points. The pain score in the CBD group was lower compared with placebo on day 5, whereas TA reduced pain more than placebo on day 4, 5, and 7. The subjects receiving CBD reported higher satisfaction than placebo. However, the OHIP-14 scores were comparable among the interventions.

CONCLUSIONS: Topical 0.1% CBD reduced ulcer size and accelerated ulcer healing without side effects. CBD exerted anti-inflammatory effects in the early stage and an analgesic effect in the late RAU stage. Thus, topical 0.1% CBD might be more appropriate for RAU patients who decline to take topical steroids, except for cases where CBD is contraindicated.

TRIAL REGISTRATION: Thai Clinical Trials Registry (TCTR) Number TCTR20220802004. Retrospectively registered on 02/08/2022.

PMID:36803360 | DOI:10.1186/s12906-023-03886-0

Cureus. 2022 Dec 17;14(12):e32622. doi: 10.7759/cureus.32622. eCollection 2022 Dec.

ABSTRACT

Medical marijuana treatment for migraine is becoming more common, although the legality and societal acceptance of marijuana for medical purposes in the United States have been challenged by the stigma attached to it as a recreational drug. These substances function to reduce nociception and decrease the frequency of migraine by having an impact on the endocannabinoid system. Our study reviewed the clinical response, dosing, and side effects of marijuana in migraine management. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a literature search in PubMed, Google Scholar, and Science Direct, and nine studies were included in the systematic review. The studies demonstrated that medical marijuana has a significant clinical response by reducing the length and frequency of migraines. No severe adverse effects were noted. Due to its effectiveness and convenience, medical marijuana therapy may be helpful for patients suffering from migraines. However, additional clinical trials and observational studies with longer follow-ups are required to study the efficacy and safety of the drug.

PMID:36660507 | PMC:PMC9845509 | DOI:10.7759/cureus.32622

Reg Anesth Pain Med. 2022 Dec 5:rapm-2021-103431. doi: 10.1136/rapm-2021-103431. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic neuropathic pain is often debilitating and can have a significant impact on sleep health and quality of life. There is limited information on the impact of cannabinoids on sleep health when treating neuropathic pain.

OBJECTIVE: The objectives of this systematic review and meta-analysis were to determine the effect of cannabinoids on sleep quality, pain intensity, and patient impression of treatment efficacy in patients with neuropathic pain.

EVIDENCE REVIEW: Nine available medical literature databases were searched for randomized controlled trials comparing synthetic and natural cannabinoids to placebo in patients with neuropathic pain syndromes. Data on validated tools for sleep quality, pain intensity, patients' global impression of change (PGIC), and incidence of adverse effects of cannabinoids were extracted and synthesized.

FINDINGS: Of the 3491 studies screened, eight randomized controlled trials satisfied the inclusion criteria for this review. Analyses were performed using R -4.1.2. using the metafor package and are interpreted using alpha=0.05 as the threshold for statistical significance. Validated measures for sleep health were not used in most studies. Meta-analysis of data from six studies showed that cannabinoids were associated with a significant improvement in sleep quality (standardized mean difference (SMD): 0.40; 95% CI: 0.19 to -0.61, 95% prediction interval (PI): -0.12 to 0.88, p-value=0.002, I²=55.26, τ²=0.05, Q-statistic=16.72, GRADE: moderate certainty). Meta-analysis of data from eight studies showed a significant reduction in daily pain scores in the cannabinoid (CB) group (SMD: -0.55, 95% CI:-0.69 to -0.19, 95% PI: -1.51 to 0.39, p=0.003, I²=82.49, τ²=0.20, Q-statistic=47.69, GRADE: moderate certainty). However, sleep health and analgesic benefits were associated with a higher likelihood of experiencing daytime somnolence, nausea, and dizziness.

CONCLUSIONS: Cannabinoids have a role in treating chronic neuropathic pain as evidenced by significant improvements in sleep quality, pain intensity, and PGIC. More research is needed to comprehensively evaluate the impact of cannabinoids on sleep health and analgesic efficacy.

PROSPERO REGISTRATION NUMBER: CRD42017074255.

PMID:36598058 | DOI:10.1136/rapm-2021-103431

J Tradit Complement Med. 2022 Oct 12;13(1):30-38. doi: 10.1016/j.jtcme.2022.10.004. eCollection 2023 Jan.

ABSTRACT

BACKGROUND AND AIM: Cannabis sativa L. is a medicinal plant with a long history. Phyto-cannabinoids are a class of compounds from C. sativa L. with varieties of structures. Endocannabinoids exist in the human body. This article provides an overview of natural cannabinoids (phyto-cannabinoids and endocannabinoids) with an emphasis on their pharmacology activities.

EXPERIMENTAL PROCEDURE: The keywords "Cannabis sativa L″, "cannabinoids", and "central nervous system (CNS) diseases" were used for searching and collecting pieces of literature from PubMed, ScienceDirect, Web of Science, and Google Scholar. The data were extracted and analyzed to explore the effects of cannabinoids on CNS diseases.

RESULT AND CONCLUSION: In this paper, schematic diagrams are used to intuitively show the phyto-cannabinoids skeletons' mutual conversion and pharmacological activities, with special emphasis on their relevant pharmacological activities on central nervous system (CNS) diseases. It was found that the endocannabinoid system and microglia play a crucial role in the treatment of CNS diseases. In the past few years, pharmacological studies focused on Δ⁹-THC, CBD, and the endocannabinoids system. It is expected to encourage new studies on a more deep exploration of other types of cannabinoids and the mechanism of their pharmacological activities in the future.

PMID:36685079 | PMC:PMC9845650 | DOI:10.1016/j.jtcme.2022.10.004

Int J Mol Sci. 2022 Dec 19;23(24):16201. doi: 10.3390/ijms232416201.

ABSTRACT

Dysmenorrhoea effects up to 90% of women of reproductive age, with medical management options including over-the-counter analgesia or hormonal contraception. There has been a recent surge in medicinal cannabis research and its analgesic properties. This paper aims to critically investigate the current research of medicinal cannabis for pain relief and to discuss its potential application to treat dysmenorrhoea. Relevant keywords, including medicinal cannabis, pain, cannabinoids, tetrahydrocannabinol, dysmenorrhoea, and clinical trial, have been searched in the PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library (Wiley) databases and a clinical trial website (clinicaltrials.gov). To identify the relevant studies for this paper, 84 papers were reviewed and 20 were discarded as irrelevant. This review critically evaluated cannabis-based medicines and their mechanism and properties in relation to pain relief. It also tabulated all clinical trials carried out investigating medicinal cannabis for pain relief and highlighted the side effects. In addition, the safety and toxicology of medicinal cannabis and barriers to use are highlighted. Two-thirds of the clinical trials summarised confirmed positive analgesic outcomes, with major side effects reported as nausea, drowsiness, and dry mouth. In conclusion, medicinal cannabis has promising applications in the management of dysmenorrhoea. The global medical cannabis market size was valued at USD 11.0 billion in 2021 and is expected to expand at a compound annual growth rate (CAGR) of 21.06% from 2022 to 2030. This will encourage academic as well as the pharmaceutical and medical device industries to study the application of medical cannabis in unmet clinical disorders.

PMID:36555842 | PMC:PMC9780805 | DOI:10.3390/ijms232416201

Drug Alcohol Depend. 2022 Nov 18;241:109702. doi: 10.1016/j.drugalcdep.2022.109702. Online ahead of print.

ABSTRACT

BACKGROUND: While six U.S. states have already officially authorized cannabinoids to substitute opioids and treat opioid use disorder, the therapeutic benefits of cannabinoids remain unclear, especially when weighted against their adverse effects.

METHODS: We conducted a systematic review of studies examining the association between opioid withdrawal and cannabis use or delta-9-tetrahydrocannabinol (THC) administration. We searched multiple databases from inception to July 30, 2022, and assessed study quality.

RESULTS: Eleven studies were identified, with a total of 5330 participants, of whom 64 % were male. Nine observational studies examined the association between cannabis use and opioid withdrawal. Two randomized, placebo-controlled clinical trials (RCTs) investigated the withdrawal-alleviating effects of dronabinol, a synthetic form of THC. Four observational studies found an association between cannabis use and the alleviation of opioid withdrawal; one reported exacerbation of opioid withdrawal symptoms; and four reported no association. RCTs reported that THC alleviated opioid withdrawal, albeit with dose-dependent increases in measures of abuse liability, dysphoria, and tachycardia. There was high heterogeneity in measurements of opioid withdrawal and the type and dose of opioid at baseline.

CONCLUSIONS: Although there is preliminary evidence that cannabis and its main psychoactive constituent, THC, may alleviate opioid withdrawal, these effects are likely to have a narrow therapeutic window. Further, the potential of cannabinoids to alleviate opioid withdrawal is determined by complex interactions between patient characteristics and pharmacological factors. Collectively, these findings have clinical, methodological, and mechanistic implications for treating opioid withdrawal during cannabinoid use, and for efforts to alleviate opioid withdrawal using non-opioid therapeutics.

PMID:36434879 | DOI:10.1016/j.drugalcdep.2022.109702

JAMA Netw Open. 2022 Nov 1;5(11):e2243848. doi: 10.1001/jamanetworkopen.2022.43848.

ABSTRACT

IMPORTANCE: Persistent pain is a common and disabling health problem that is often difficult to treat. There is an increasing interest in medicinal cannabis for treatment of persistent pain; however, the limited superiority of cannabinoids over placebo in clinical trials suggests that positive expectations may contribute to the improvements.

OBJECTIVE: To evaluate the size of placebo responses in randomized clinical trials in which cannabinoids were compared with placebo in the treatment of pain and to correlate these responses to objective estimates of media attention.

DATA SOURCES: A systematic literature search was conducted within the MEDLINE and Embase databases. Studies published until September 2021 were considered.

STUDY SELECTION: Cannabinoid studies with a double-blind, placebo-controlled design with participants 18 years or older with clinical pain of any duration were included. Studies were excluded if they treated individuals with HIV/AIDS or severe skin disorders.

DATA EXTRACTION AND SYNTHESIS: The study followed the Preferred Reporting Items for Systematic Review and Meta-analyses reporting guideline. Data were extracted by independent reviewers. Quality assessment was performed using the Risk of Bias 2 tool. Attention and dissemination metrics for each trial were extracted from Altmetric and Crossref. Data were pooled and analyzed using a random-effects statistical model.

MAIN OUTCOMES AND MEASURES: Change in pain intensity from before to after treatment, measured as bias-corrected standardized mean difference (Hedges g).

RESULTS: Twenty studies, including 1459 individuals (mean [SD] age, 51 [7] years; age range, 33-62 years; 815 female [56%]), were included. Pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean [SE] Hedges g, 0.64 [0.13]; P < .001). Trials with low risk of bias had greater placebo responses (q1 = 5.47; I2 = 87.08; P = .02). The amount of media attention and dissemination linked to each trial was proportionally high, with a strong positive bias, but was not associated with the clinical outcomes.

CONCLUSIONS AND RELEVANCE: Placebo contributes significantly to pain reduction seen in cannabinoid clinical trials. The positive media attention and wide dissemination may uphold high expectations and shape placebo responses in future trials, which has the potential to affect the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief.

PMID:36441553 | DOI:10.1001/jamanetworkopen.2022.43848

J Sleep Res. 2022 Dec 20:e13793. doi: 10.1111/jsr.13793. Online ahead of print.

NO ABSTRACT

PMID:36539991 | DOI:10.1111/jsr.13793

Cannabis Cannabinoid Res. 2022 Dec 6. doi: 10.1089/can.2022.0185. Online ahead of print.

NO ABSTRACT

PMID:36475998 | DOI:10.1089/can.2022.0185

Expert Rev Neurother. 2022 Dec 12:1-10. doi: 10.1080/14737175.2022.2155139. Online ahead of print.

NO ABSTRACT

PMID:36503404 | DOI:10.1080/14737175.2022.2155139

J Sleep Res. 2022 Dec 20:e13793. doi: 10.1111/jsr.13793. Online ahead of print.

NO ABSTRACT

PMID:36539991 | DOI:10.1111/jsr.13793

Front Pharmacol. 2022 Oct 25;13:989717. doi: 10.3389/fphar.2022.989717. eCollection 2022.

ABSTRACT

Despite the significant advances in neurology, the cure for neurodegenerative conditions remains a formidable task to date. Among various factors arising from the complex etiology of neurodegenerative diseases, neuroinflammation and oxidative stress play a major role in pathogenesis. To this end, some phytocannabinoids isolated from Cannabis sativa (widely known as marijuana) have attracted significant attention as potential neurotherapeutics. The profound effect of ∆⁹-tetrahydrocannabinol (THC), the major psychoactive component of cannabis, has led to the discovery of the endocannabinoid system as a molecular target in the central nervous system (CNS). Cannabidiol (CBD), the major non-psychoactive component of cannabis, has recently emerged as a potential prototype for neuroprotective drug development due to its antioxidant and anti-inflammatory properties and its well-tolerated pharmacological behavior. This review briefly discusses the role of inflammation and oxidative stress in neurodegeneration and demonstrates the neuroprotective effect of cannabidiol, highlighting its general mechanism of action and disease-specific pathways in Parkinson's disease (PD) and Alzheimer's disease (AD). Furthermore, we have summarized the preclinical and clinical findings on the therapeutic promise of CBD in PD and AD, shed light on the importance of determining its therapeutic window, and provide insights into identifying promising new research directions.

PMID:36386183 | PMC:PMC9640911 | DOI:10.3389/fphar.2022.989717