Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Efficacy of cannabidiol alone or in combination with Δ-9-tetrahydrocannabinol for the management of substance use disorders: An umbrella review of the evidence

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“Background and aims: Substance use disorders (SUD) lead to a high burden of disease, yet treatment options are limited. Cannabidiol (CBD) is being investigated as a potential therapeutic target due to its pharmacological properties and mode of action in the endocannabinoid system. Recent systematic reviews (SR) on CBD and SUDs have shown inconsistent results. The objective of this umbrella review was to determine whether CBD alone or in combination with Δ-9-tetrahydrocannabinol (THC) is effective for managing and treating SUDs.

Methods: Following a registered protocol, we searched PubMed, Web of Science and Epistemonikos databases for SRs, with or without a meta-analysis, of randomized controlled trials focusing on interventions dispensing CBD, alone or in combination with THC, to treat SUDs, published from 1 January 2000 to 15 October 2024. Screening, data extraction and quality assessment with the AMSTAR 2 tool were performed by two researchers in parallel and duplicated.

Results: 22 SRs were included, 5 of which performed a meta-analysis. We found mixed evidence regarding the efficacy of CBD to manage and treat SUDs. Findings were interpreted in light of the quality of the SRs. Nabiximols, which contains CBD and THC, demonstrated positive effects on cannabis withdrawal and craving symptoms. Evidence supporting the efficacy of CBD is limited and inconclusive for abstinence, reduction or cessation of use of cannabis, tobacco, alcohol, opiates and other psychoactive substances.

Conclusion: Cannabidiol (CBD) monotherapy does not appear to be efficacious for treatment of substance use disorders. CBD primarily exhibits effects on cannabis withdrawal and craving when combined with Δ-9-tetrahydrocannabinol (THC). Existing data on the efficacy of CBD alone with regard to other outcomes related to substance use disorders are limited.”

https://pubmed.ncbi.nlm.nih.gov/39947878/

“This umbrella review does not suggest any efficacy of CBD monotherapy as a therapeutic agent in SUDs. CBD primarily exhibits effects on cannabis withdrawal and craving symptoms when combined with THC in nabiximols. The CBD:THC 1:1 effects suggest that the potential benefits observed in cannabis withdrawal and craving may be because of THC, with CBD providing no additional benefit. We found no evidence for CBD alone, in the absence of THC, in managing cannabis and other SUDs. “

https://onlinelibrary.wiley.com/doi/10.1111/add.16745

Therapeutic potential of cannabinoids in neurological conditions: a systematic review of clinical trials

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“Overview: Cannabinoids have gained increasing attention for their therapeutic potential in treating several neurological conditions, including neurodegenerative diseases, chronic pain, and epilepsy. This review aims to assess the current clinical trials investigating cannabinoids, primarily Tetrahydrocannabinol and Cannabidiol, for neurological disorders. This review will aim to highlight the efficacy, safety, and outcome measures used in these trials.

Methods: Clinical trials were identified using ClinicalTrials.gov, focusing on studies that examined the effects of cannabinoids in treating neurological conditions. All trials that fulfilled the following criteria were included: Phase 1–4, focused on cannabinoids as primary intervention, and measured relevant outcomes such as pain relief, cognitive function, or spasticity reduction. Data on conditions, interventions, primary and secondary outcomes, and trial phases were extracted and analysed.

Results: A total of 47 clinical trials were identified, including different neurological conditions. The most frequently studied conditions were Multiple Sclerosis, Fibromyalgia, and Parkinson’s Disease. Most trials were in Phase 2, with the primary outcome measures focused on pain management, spasticity, and cognitive function. Secondary outcomes included safety and tolerability measures.

Conclusion: The review highlights the broad therapeutic potential of cannabinoids in neurology, with promising results in symptom management for conditions like Multiple Sclerosis and Fibromyalgia. However, the lack of standardized study protocols, dosing, and outcome measures presents challenges for broader clinical implementation.”

“The results of this analysis showed that both CBD and THC have significant potential as therapeutic agents for neurological disorders, particularly in managing pain, motor dysfunction, and behavioural disturbances. However, their different pharmacological profiles and side effect risks mean that each cannabinoid may be better suited to different patient populations and conditions. While THC’s broader range of applications in cognitive and motor symptoms positions it as a more multipurpose treatment option, the psychoactive risks associated with its use should not be ignored. On the other hand, CBD’s safety and non-psychoactive nature make it more preferred option for managing chronic pain, but its therapeutic benefits may be more limited. Future research should focus on addressing the gaps in long-term safety and efficacy data, as well as exploring the full potential of lesser-known cannabinoids and combination therapies to further enhance the treatment of neurological disorders.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1521792/full

Amyotrophic Lateral Sclerosis, the Endocannabinoid System, and Exogenous Cannabinoids: Current State and Clinical Implications

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“A unifying mechanistic cause for amyotrophic lateral sclerosis (ALS) remains uncertain. Multiple pathophysiological processes appear to occur simultaneously.

Cannabinoids, including delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), and others found in cannabis, and cannabis extracts (CEs), appear to have activity in these pathogenic pathways, which have led to increasing interest in cannabinoids as therapeutic agents for ALS.

The use of cannabinoids as a treatment strategy is substantiated by preclinical evidence suggesting a role for the endocannabinoid system (ECS) in ALS and other neurodegenerative disorders.

Preclinical data indicate that cannabis and CEs have powerful antioxidative, anti-inflammatory, and neuroprotective effects in the SOD1G93A mouse model of ALS. The use of CEs in SOD1G93A murine models has been shown to prolong neuronal cell survival, which leads to delayed onset of the disease state, and slows progression of the disease.

Although research in humans remains limited, a few studies suggest that cannabis and CBD, in humans, provide benefits for both motor symptoms, including rigidity, cramps, and fasciculations, and non-motor symptoms including sleep quality, pain, emotional state, quality of life, and depression. There remains a need for further, well-designed clinical trials to validate further the use of an individual cannabinoid, or a combination of cannabinoids, as a disease-modifying therapy for ALS.”

https://pubmed.ncbi.nlm.nih.gov/39936266/

https://onlinelibrary.wiley.com/doi/10.1002/mus.28359

Effects of cannabis smoke and oral Δ9THC on cognition in young adult and aged rats

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“Rationale: With increasing legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis can impair cognition in young adults, it is critically important to understand how its consumption interacts with the cognitive profile of aged subjects, who are already at increased risk of decline.

Objectives: The current study was designed to determine how cannabis influences multiple forms of cognition in young adult and aged rats of both sexes when delivered via two translationally-relevant routes of administration.

Methods: Rats were exposed acutely to cannabis smoke or chronically to oral Δ9-tetrahydrocannabinol (Δ9THC), followed by cognitive testing.

Results: Acute cannabis smoke enhanced prefrontal cortex-dependent working memory accuracy in aged males, but impaired accuracy in aged females, while having no effects in young adults of either sex. In contrast, the same cannabis smoke regimen had minimal effects on a hippocampus-dependent trial-unique non-matching to location mnemonic task, irrespective of age or sex. Chronic oral consumption of Δ9THC enhanced working memory in aged rats of both sexes, while having no effects in young adults. In contrast, the same Δ9THC regimen did not affect spatial learning and memory in either age group. Minimal age differences were observed in Δ9THC pharmacokinetics with either route of administration.

Conclusions: The results show that cannabis and Δ9THC can attenuate working memory impairments that emerge in aging. While these enhancing effects do not extend to hippocampus-dependent cognition, cannabis does not appear to exacerbate age-associated impairments in this cognitive domain.”

https://pubmed.ncbi.nlm.nih.gov/39918581/

https://link.springer.com/article/10.1007/s00213-025-06754-6

Acute and prolonged toxicity assessment of Cannabis sativa extract in rodents and lagomorphs

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“Cannabinoids offer a novel pharmacotherapeutic approach and can complement other medications to address unmet clinical needs in numerous patients, which has led to a global increase in the use of these products.

No significant safety concerns have been identified in preclinical studies involving CBD and THC. However, the available data on the toxicity of combined CBD and THC are still inconclusive. Evaluating full-spectrum Cannabis sativa extracts is even more complex since whole extracts and isolated phytomolecules do not act in the same way.

Given the growing interest in cannabinoid-containing products for human use and the fact that most cannabis treatments utilize entire inflorescence rather than isolated compounds, the current studies aim to evaluate the preclinical safety of a full-spectrum composition (THC, CBD, minor cannabinoids, terpenes, and flavonoids) Cannabis sativa extract (CSE).

This research includes acute (single dose, with animals monitored for 14 days to assess potential effects) and long-term treatments (6 months for rodents and 9 months for rabbits) to assess safety and tolerance.

This study demonstrates that a full-spectrum Cannabis sativa extract has a favorable safety profile in both acute and prolonged toxicity studies in rodents and rabbits.

In acute toxicity tests, the extract did not show any significant behavioral or physiological changes after oral or intraperitoneal administration. Additionally, administering the extract acutely to rabbits had minimal impact on the central nervous, cardiovascular, and respiratory systems, with only a temporary reduction in motor activity at the highest dose.

Prolonged administration of 6 months in rats and 9 months in rabbits did not lead to significant changes in organ histopathology, body weight, or behavior.

Although liver enzymes were elevated at the highest doses, other biochemical and hematological parameters remained unchanged. CSE was well-tolerated, as no serious adverse effects were observed; however, a reduction in motor activity was noted in the highest dose group, highlighting the need for further investigation, which is proposed for future studies.”

https://pubmed.ncbi.nlm.nih.gov/39917037/

https://www.sciencedirect.com/science/article/pii/S2214750025000368?via%3Dihub

Advances in cannabinoid receptors pharmacology: from receptor structural insights to ligand discovery

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“The medicinal and recreational uses of Cannabis sativa have been recognized for thousands of years.

Today, cannabis-derived medicines are used to treat a variety of conditions, including chronic pain, epilepsy, multiple sclerosis, and chemotherapy-induced nausea. However, cannabis use disorder (CUD) has become the third most prevalent substance use disorder globally.

Cannabinoid receptors are the primary targets that mediate the effects of cannabis and its analogs. Despite their importance, the mechanisms of modulation and the full therapeutic potential of cannabinoid receptors remain unclear, hindering the development of the next generation of cannabinoid-based drugs.

This review summarizes the discovery and medicinal potential of phytocannabinoids and explores the distribution, signaling pathways, and functional roles of cannabinoid receptors. It also discusses classical cannabinoid drugs, as well as agonists, antagonists, and inverse agonists, which serve as key therapeutic agents.

Recent advancements in the development of allosteric drugs are highlighted, with a focus on positive and negative allosteric modulators (PAMs and NAMs) that target CB1 and CB2 receptors. The identification of multiple allosteric sites on the CB1 receptor and the structural basis for allosteric modulation are emphasized, along with the structure-based discovery of ago-BAMs for CB1.

This review concludes by examining the future potential of allosteric modulators in cannabinoid drug development, noting that ongoing progress in cannabinoid-derived drugs continues to open new avenues for therapeutic use and paves the way for future research into their full medicinal potential.”

https://pubmed.ncbi.nlm.nih.gov/39910211/

https://www.nature.com/articles/s41401-024-01472-9

The effects of recreational cannabis laws on alcohol and tobacco use among US adults, 2012 to 2022

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“Introduction: Many states have legalized cannabis for medicinal and recreational purposes in the past decade. However, it is unclear how recreational cannabis laws (RCLs) may affect alcohol and tobacco use among adults.

Methods: This is a cross-sectional study of 4.8 million adults from the 2012-2022 Behavioral Risk Factor Surveillance System. A difference-in-differences approach was used to examine the impact of RCLs on the use of alcohol and tobacco, adjusting for individual-level characteristics and time-varying state-level factors. The analyses were performed in 2024.

Results: Three alcohol use outcomes (current drinking, binge drinking, and heavy drinking) and two tobacco use outcomes (current tobacco use and smokeless tobacco use) were examined. Considering passage of cannabis laws as RCL implementation,

RCLs were not associated with any alcohol or tobacco use outcomes in the fully adjusted model. However, considering operational dispensary as RCL implementation, RCLs were associated with a decrease of 0.95 percentage point (95% CI, 1.80 to 0.09) in current drinking and a decrease of 0.48 percentage point (95% CI, 0.85 to 0.10) in current cigarette use.

Subgroup analysis showed that RCLs were associated with reductions in current drinking, binge drinking, and current cigarette use in multiple groups. However, RCLs were associated with increases in current smokeless tobacco use for some groups.

Conclusions: The findings suggest that while the overall effects of RCLs on the use of alcohol and tobacco may be limited, there are heterogeneous associations of RCLs with drinking and smoking by age, sex, race and ethnicity, education, and income.”

https://pubmed.ncbi.nlm.nih.gov/39909135/

https://www.ajpmonline.org/article/S0749-3797(25)00038-8/abstract

Study rationale and baseline data for pilot trial of dronabinol adjunctive treatment of agitation in Alzheimer’s dementia (THC-AD)

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“Agitation is a common complication of Alzheimer’s dementia (Agit-AD) associated with substantial morbidity, high healthcare service utilization, and adverse emotional and physical impact on care partners. There are currently no FDA-approved pharmacological treatments for Agit-AD.

We present the study design and baseline data for an ongoing multisite, three-week, double-blind, placebo-controlled, randomized clinical trial of dronabinol (synthetic tetrahydrocannabinol [THC]), titrated to a dose of 10 mg daily, in 80 participants to examine the safety and efficacy of dronabinol as an adjunctive treatment for Agit-AD.

Preliminary findings for 44 participants enrolled thus far show a predominately female, white sample with advanced cognitive impairment (Mini Mental Status Examination mean 7.8) and agitation (Neuropsychiatric Inventory-Clinician Agitation subscale mean 14.1). Adjustments to study design in light of the COVID-19 pandemic are described.

Findings from this study will provide guidance for the clinical utility of dronabinol for Agit-AD. ClinicalTrials.gov Identifier: NCT02792257.”

https://pubmed.ncbi.nlm.nih.gov/39890402/

https://www.intpsychogeriatrics.org/article/S1041-6102(25)00261-3/fulltext

“Clinical Trial Shows Synthetic Cannabis Reduces Agitation in Alzheimer’s Disease”

https://www.hopkinsmedicine.org/news/newsroom/news-releases/2024/10/clinical-trial-shows-synthetic-cannabis-reduces-agitation-in-alzheimers-disease

“Cannabidiol for behavior symptoms in Alzheimer’s disease (CANBiS-AD): a randomized, double-blind, placebo-controlled trial”

https://pubmed.ncbi.nlm.nih.gov/39890408/

The comparative effectiveness of medicinal cannabis for chronic pain versus prescription medication treatment

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“Reviews of the effectiveness of medicinal cannabis for chronic pain vary in their conclusions. IASP has identified that a key missing evidence in this debate is data from observational cohort studies, analyzed with comparative effectiveness methods.

In a medically supervised context to the use of marijuana for chronic pain, we identified 440 patients certified for medical marijuana by pain specialists in a single healthcare system. They were characterized by a battery of patient-reported outcomes stored electronically in the University of Pittsburgh Patient Outcomes Repository for Treatment (PORT).

At 3 months, 38.6% were responders, based on clinically meaningful improvements in pain, function, or global impression of change, and maintained this response at 6 months. In the 157 patients who were coprescribed opioids, at 6 months there was a mean 39.3% decrease in morphine milligram equivalents (P < 0.05 for the difference vs baseline).

In addition, 8114 patients treated in the same pain clinics with prescription pain medications instead (nonopioid or opioid) during the same timeframe were selected from PORT as a control group for comparison. They had a 34.9% rate of response at 3 months. Using the causal inference method of stratified modeling, logistic regression revealed an odds ratio of 2.6 in favor of medical marijuana vs medication treatment (P < 0.01). Potential harms data were not available in the PORT registry.

Medical marijuana was comparatively more effective than prescription medications for the treatment of chronic pain at 3 months, although the populations compared were slightly different.”

https://pubmed.ncbi.nlm.nih.gov/39878633/

https://journals.lww.com/pain/abstract/9900/the_comparative_effectiveness_of_medicinal.807.aspx

Exploring the diversity of cannabis cannabinoid and non-cannabinoid compounds and their roles in Alzheimer’s disease: A review

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“Cannabis sativa is recognized for its chemical diversity and therapeutic potential, particularly in addressing neurodegenerative diseases such as Alzheimer’s disease (AD). Given the complexity of AD, where single-target therapies often prove inadequate, a multi-target approach utilizing cannabis-derived compounds may offer promising alternatives.

This review first highlights the chemical diversity of cannabis by categorizing its compounds into cannabinoids and non-cannabinoids. It then examines studies investigating the effects of these compounds on AD-related pathological features.

By synthesizing existing knowledge, identifying research gaps, and facilitating comparative analysis, this review aims to advance future research and understanding. It underscores cannabis’s potential as a multi-target therapeutic strategy for AD, contributing valuable insights to ongoing scientific discussions.”

https://pubmed.ncbi.nlm.nih.gov/39866750/

“Cannabis sativa exhibits rich chemical diversity, categorized into cannabinoid and non-cannabinoid compounds.”

“The plant’s therapeutic potential is particularly relevant for treating neurodegenerative diseases like AD.”

“The discovery of the endocannabinoid system underscores the importance of cannabis-derived compounds in AD research.”

“A multi-target approach with cannabis compounds may overcome the limitations of single-target therapies in AD.”

“The review synthesizes existing research, identifies gaps, and aims to improve future studies on cannabis and AD.”

https://www.ibroneuroreports.org/article/S2667-2421(24)00119-2/fulltext