“Pain management costs the world billions of dollars each year, and there are limited nonopioid options to treat people suffering from chronic pain. Opioids are excellent analgesics but are liable to abuse and fatal overdoses. This Microperspective summarizes challenges and opportunities pertaining to creating nonopioid drugs that could be used to treat chronic pain, substance abuse, fatty liver, or obesity by targeting the cannabinoid receptor type 1 (CB1).”
“Objective: Cannabis use is strongly linked with heavy drinking and worse alcohol treatment outcomes; however, it may also contribute to decreased alcohol consumption. To date, no human studies have established a causal effect of cannabis on alcohol motivation. The aim of this double-blind crossover randomized clinical trial was to examine dose-dependent acute effects of delta-9-tetrahydrocannabinol (THC) on alcohol craving and consumption.
Methods: Across three experimental days, 157 participants reporting heavy alcohol use and cannabis use two or more times weekly were randomized to smoke cannabis cigarettes containing 7.2% THC, 3.1% THC, or 0.03% THC (placebo), followed by exposures to neutral and personalized alcohol cues and an alcohol choice task for alcohol self-administration. A total of 138 participants completed two or more experimental sessions (mean age, 25.6 years [SD=5.1]; 35% women; 45% racial/ethnic minorities). Primary outcomes included craving, Alcohol Craving Questionnaire-Short Form, Revised (ACQ-SF-R), and an alcohol urge question; the secondary outcome was percent of total available milliliters of alcohol consumed.
Results: There were no significant effects of cannabis on ACQ-SF-R ratings after smoking and during alcohol cue exposure, but 7.2% THC reduced alcohol urge immediately after smoking. Participants consumed significantly less alcohol after smoking cannabis with 3.1% THC and 7.2% THC, reducing consumption by 19% and 27%, respectively.
Conclusions: Following overnight cannabis abstinence, smoking cannabis acutely decreased alcohol consumption compared to placebo. Further controlled research on a variety of cannabinoids is needed to inform clinical alcohol treatment guidelines.”
https://pubmed.ncbi.nlm.nih.gov/41254853
“These data provide preliminary evidence that cannabis may reduce alcohol consumption under some conditions”
“Endometriosis is a chronic, inflammatory, and multifactorial disease characterized by the presence of endometrial tissue outside the uterine cavity, often associated with debilitating symptoms. It affects approximately 10% of women of reproductive age and is also related to infertility. Endometriosis can be classified as peritoneal, ovarian, or deep endometriosis, with primary symptoms including chronic pelvic pain, dysmenorrhea, and dyspareunia. Diagnosis and treatment are challenging, with laparoscopy and biopsy of ectopic tissue being the gold standard.
Cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC) are two major cannabinoids found in the Cannabis sativa plant, widely known for their medicinal properties.
An experimental study conducted in rats demonstrated the anti-inflammatory, antioxidant, and antiangiogenic effects of intraperitoneal CBD use in the treatment of endometriosis. The objective of the present study was to conduct a literature review on the therapeutic potential of Cannabidiol (CBD) and ∆9-Tetrahydrocannabinol (THC) in the signs and symptoms of endometriosis. Research on PubMed, Embase, and Scopus platforms was conducted to determine the reproducibility and safety of treatment in humans, including dosage and administration route, as the current use is off-label.”
“Although tetrahydrocannabinol (THC) and cannabidiol (CBD) have been individually studied for their neuroprotective roles, few studies have addressed the effects of their balanced 1:1 formulation Satinex (STX) under pathologic conditions like hypoxia. Moreover, the effect of STX on embryonic neural stem/progenitor cells (ENS/PCs) derived from the rat embryonic brain, which are highly vulnerable during early development, remains unexplored.
Considering the pivotal role of hypoxia in numerous neuropathological situations, this study examined the impact of STX on rat ENS/PCs exposed to chemically induced hypoxia.
ENS/PCs were isolated from rat embryos and subjected to hypoxia using 100 µM cobalt (II) chloride hexahydrate (CoCl₂0.6 H₂O) for 48 h. Cytotoxic activity of STX andCoCl2was assessed using the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2 H-tetrazolium (MTT) assay, while stem cell identity was confirmed via flow cytometry (Nestin, SOX2). STX (0.1 and 0.5 µM) was applied under both normoxic and hypoxic conditions. Expression levels of hypoxia-inducible factor 1-alpha (Hif1α) mRNA, autophagy markers (Beclin-1, microtubule-associated protein 1 light chain 3-II [LC3-II]), and pro-inflammatory proteins nuclear factor kappa B [NF-κB], Toll-like receptor 2 [TLR2], Toll-like receptor 4 [TLR4]) were assessed using reverse transcription polymerase chain reaction (RT-PCR) and western blot techniques following STX treatment.
Based on flow cytometric assays, over 70% of cultivated cells were positive for Nestin and SOX2. Hypoxia significantly reduced cell viability and proliferation, accompanied by increased Hif1α mRNA expression. Treatment with STX (0.1 µM and 0.5 µM) significantly reversed these changes, restoring cell viability and proliferation while reducing Hif1α levels. Hypoxia also elevated autophagy markers (Beclin-1, LC3-II) and pro-inflammatory proteins (NF-κB, TLR2, TLR4), which STX suppressed in a dose-dependent manner.
This study provides novel evidence that STX mitigates hypoxia-induced neural damage by downregulating Hif1α and its downstream inflammatory and autophagic signaling pathways. The use of a clinically relevant cannabinoids mixture and a developmentally sensitive cell model underline the translational potential of balanced THC/CBD formulations in the treatment of hypoxia-related neurodegenerative and neurodevelopmental conditions.”
https://pubmed.ncbi.nlm.nih.gov/41240218
https://link.springer.com/article/10.1007/s12640-025-00770-2
“Pharmacological interventions that treat core and co-occurring features of autism spectrum disorder (ASD) are a persistent unmet need.
As such, use of cannabis to manage ASD features is common in the autistic community. Yet, few studies have examined the acute effects of cannabis on symptoms associated with ASD. Therefore, we measured changes in symptom ratings from before to after cannabis use in a sample of 111 self-identified autistic adults.
Anonymized archival data sourced from the Strainprint® app were analyzed. A subset of tracked information that reflected changes in core and co-occurring symptoms associated with ASD (i.e., Sensory Sensitivity, Repetitive Behaviors, Mental Control, and Negative Affect) were used to assess the impacts of cannabis on symptom severity.
Overall, symptom severity ratings were reduced by 73.09% from before to after cannabis use. More severe symptoms were associated with greater reductions in severity ratings after use.
Higher doses predicted greater reductions in severity of Repetitive Behaviors, Mental Control, and Negative Affect but dose of cannabis used to manage all symptoms remained static across time.
Results from this first empirical examination of the perceived acute effects of cannabis in autistic adults suggest that cannabis provides temporary relief from symptoms associated with ASD.”
https://pubmed.ncbi.nlm.nih.gov/41233406/
“The present study represents the first to demonstrate acute perceived beneficial effects of inhaled cannabis on core and co-occurring symptoms associated with ASD in a large adult sample.”
“These findings indicate that well-powered placebo-controlled trials are warranted to examine the acute effects of various cannabinoids and manipulations of the endocannabinoid system on ASD symptoms.”
“In sum, data from clinical trials of children and adolescents presents an evidence base that supports a continued focus on the impact of CBD on ASD features, while the present data from cannabis-using autistic adults indicates that a sole focus on CBD may not fully capture the potential impact of cannabinoids as a pharmacological intervention for adults with ASD. Thus, additional placebo-controlled clinical trials are needed where THC, CBD, and other non-intoxicating cannabinoids (e.g., cannabigerol), terpenes, and/or medications that modulate the functioning of the endocannabinoid system are administered to autistic adults to determine their relative effects on symptoms associated with ASD.”
“Objecives: Approximately 80 % of people living with HIV (PLWH) develop chronic pain and preclinical studies support the involvement of the HIV-1 regulatory protein, trans-activator of transcription (Tat). Phytocannabinoids may attenuate pain in PLWH; however, these data are controversial, and the biological mechanisms are difficult to untangle from psychosocial factors in people.
Methods: We have examined the therapeutic capacity of minor phytocannabinoids to attenuate Tat-promoted visceral hyperalgesia (acetic acid writhing assay) and reflexive nociception (warm water tail flick assay) in transgenic mice. We hypothesized that conditional expression of Tat1-86 in male and female mice [Tat(+) mice] would amplify pain responses compared to controls [Tat(-) mice], and that phytocannabinoids could ameliorate these effects.
Results: Irrespective of sex, Tat(+) mice demonstrated greater visceral pain responses than did Tat(-) controls. The phytocannabinoids, cannabigerolic acid (CBGA), cannabidiol (CBD), and cannabinol (CBN), attenuated Tat-induced visceral pain in both males and females. However, the effectiveness of these cannabinoids varied by sex with CBN being more efficacious in males, while cannabigerol (CBG) alleviated visceral pain only in Tat(+) females. Cannabidiolic acid (CBDA) and cannabidivarin (CBDV) were not effective in either sex. CBGA and CBG were also efficacious in the tail flick test among Tat(-) males and females, but demonstrated only small, sex-dependent effects to reverse Tat-induced nociception. CBD and CBN exerted little-to-no efficacy in this test.
Conclusions: These data suggest that phytocannabinoids exert analgesia for HIV-related pain, potentially aiding in the development of personalized pain management strategies.”
https://pubmed.ncbi.nlm.nih.gov/41221301/
“Overall, PLWH are more vulnerable to the development of chronic pain, resulting in physical disability and a reduced quality of life. The current pharmacological treatments for managing HIV-related pain lack efficacy and are associated with the risk of substance abuse. The medicinal use of non-psychoactive cannabis constituents for pain management might greatly benefit this population which is at a greater risk for opioid addiction and substance abuse.”
https://www.degruyterbrill.com/document/doi/10.1515/nipt-2024-0025/html
“Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) can greatly impair function, leading to disability or truncated treatment in cancer patients. Previous animal studies show that cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC) can ameliorate CIPN. This study assessed the effect of combined CBD and THC on CIPN symptoms amongst cancer patients treated with taxane- or platinum-based agents.
Materials and methods: This 12-week randomized, double-blind, placebo-controlled trial included participants with nonmetastatic breast, colorectal, endometrial, or ovarian cancer experiencing grade 2-3 CIPN. The active group received CBD (125.3-135.9 mg) combined with THC (6.0-10.8 mg) in gelcaps. The Quality-of-Life Questionnaire-CIPN twenty-item scale (QLQ-CIPN20) sensory subscale was used as the primary outcome. Additional outcomes assessed pain, sleep, and function. Neurologic exams evaluated touch, pressure, and vibration sense. Following the randomized controlled trial, participants were invited to enroll in a 12-week open-label observational study.
Results: Of 230 participants identified, 124 met eligibility, 54 were enrolled, 46 were randomized, and 43 completed 12 weeks of treatment. This was lower than our goal of 100 randomized participants. The mean age was 60 +/- 9 years, 88% were female, 63% had breast cancer. All participants had completed chemotherapy. The primary analysis showed no differences in outcome measures between active and placebo groups, likely due to sample size. Although an increase in bilirubin (one participant in active group, and one in placebo) and alkaline phosphatase (one participant in active group) was seen, this did not exceed the exit criteria. A secondary analysis showed that the active group experienced greater improvement in the QLQ-CIPN20 measures of sensory impairment relative to placebo (-10.4 (95% -20.5, -0.3), p = 0.044). There was also improvement in light touch and vibration sensation of the feet on neurological exam that approached significance. There was no effect on other measures, including pain, and no between-group differences in side effects. The uncontrolled observational study showed similar results.
Discussion: The primary analysis showed no between-group difference in CIPN symptoms. The secondary analysis indicated that CBD with THC could improve sensory impairment and might increase touch and vibration sense, although these findings require confirmation in a future, more fully powered study. Nonetheless, our results show that combination CBD/THC can be safely delivered to participants with CIPN and suggest that these cannabinoids should be further investigated for this indication.”
https://pubmed.ncbi.nlm.nih.gov/41211445/
“Overall, this study suggests that combination CBD/THC could help with the sensory impairment seen in CIPN. Since the disorder is prevalent and incurs significant hardship, even a modest sensory improvement could enhance patients’ quality of life, given the lack of alternatives.”
https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1590168/full
“Tetrahydrocannabinol (THC) has shown efficacy in alleviating chronic pain, particularly in disorders characterized by central sensitization. Offset analgesia (OA) and conditioned pain modulation (CPM) are key biomarkers used to evaluate central pain modulation.
This study aimed to compare the effects of THC on OA and CPM in fibromyalgia syndrome (FMS), a prototypical condition of central sensitization.
In a randomized, double-blind, placebo-controlled crossover design, 23 FMS patients participated in two experimental sessions. Each session included the McGill Pain Questionnaire, visual analogue scale (VAS) assessments, and evaluations of OA and CPM, conducted both before and after sublingual administration of either THC (0.2 mg/kg) or placebo.
THC significantly reduced spontaneous pain ratings on the McGill scale compared to both baseline and placebo (P = 0.01 and P = 0.02, respectively). THC also significantly enhanced OA relative to baseline and placebo (P = 0.04 and P = 0.008), while no effect was observed on CPM (P = 0.27). Notably, baseline OA magnitude significantly predicted THC-induced pain relief (R² = 0.404, P = 0.003), whereas CPM did not show a significant association (P = 0.121).
This is the first study to evaluate THC’s distinct effects on central pain modulation using both OA and CPM. THC selectively enhanced OA without influencing CPM, highlighting differential neural mechanisms underlying these paradigms. Furthermore, OA predicted treatment response, suggesting its potential as a biomarker for personalized cannabinoid-based therapies in FMS and other central sensitization disorders.”
https://pubmed.ncbi.nlm.nih.gov/41199355/
“Cannabis, particularly its psychoactive component delta-9-tetrahydrocannabinol (THC), has attracted increasing attention as a therapeutic option for chronic pain management. Clinically, THC has been shown to reduce pain intensity, improve quality of life and attenuate hyperalgesia in various chronic pain conditions, including neuropathic pain and fibromyalgia “
“THC is thought to exert its analgesic effects in part by modulating disrupted pain networks. Specifically, THC interacts with the endocannabinoid system.”
“To conclude, this study corroborates the possible effectiveness of THC in alleviating experimental and spontaneous pain in FMS, a study case of central sensitization, and shows an enhancement of OA responses after THC treatment in FMS patients compared to baseline and placebo.”
“This, in turn, reinforces the potential of OA as a reliable marker of pain modulation in FMS and may pave the way for personalized cannabinoid-based therapies for chronic pain in the future.”
https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00348-x
“The endocannabinoid system regulates neuronal activity and plasticity, but its role in non-mammalian vertebrates remains poorly understood.
In zebrafish (Danio rerio), the pallium processes cognitive functions such as memory, learning, and emotional behavior. This region expresses cannabinoid receptors and undergoes continuous neuronal remodeling through adult neurogenesis.
Here, we investigate whether cannabinoid receptor type 1 (CB1R) modulates synaptic activity and adult neurogenesis in zebrafish pallial circuits.
Using immunofluorescence and single-cell mRNA analysis, we mapped CB1R expression in the pallium and found it to be distributed in a scattered pattern within the dorsomedial (Dm) and dorsolateral (Dl) regions, predominantly in glutamatergic neurons.
Electrophysiological recordings showed that acute application of rimonabant, a CB1R antagonist, reduced the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) without altering intrinsic or other synaptic properties, suggesting a tonic role for CB1R in modulating synaptic transmission. Additionally, prolonged rimonabant treatment (13 days) significantly reduced ERK phosphorylation, a marker of neuronal activity, further supporting the involvement of CB1R in maintaining basal synaptic activity in the pallium.
To assess whether cannabinoid signaling shapes adult neurogenesis, we analyzed the proliferation of neural stem cells (NSCs) and maturation of adult-born neurons.
Acute phytocannabinoid exposure resulted in a reduction in NSC proliferation, specifically in the anterior Dm. To assess the neurogenic outcome, the cannabinoid treatment was administered during neuronal maturation (12-24 days after BrdU labeling).
We observed an increase in the number of 25-day-old neurons (BrdU+, HuC/D+) in both Dm and Dl regions. This effect was reverted by the CB1R antagonist rimonabant.
These results indicate that cannabinoid signaling modulates synaptic activity and neuronal integration, highlighting a conserved control of neurogenesis by the endocannabinoid system across vertebrates.”
https://pubmed.ncbi.nlm.nih.gov/41200796/
https://onlinelibrary.wiley.com/doi/10.1111/jnc.70289
“Delta-9-Tetrahydrocannabinol (∆9-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats”
https://link.springer.com/article/10.1007/s12640-017-9806-x
“Antimicrobial resistance remains a critical global health threat, driving the urgent need for novel therapeutic agents. Cannabinoids, bioactive secondary metabolites derived from Cannabis sativa, have gained attention for their promising antimicrobial properties.
This review presents the latest advances in the antimicrobial properties of cannabinoids, emphasizing their activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and selected Gram-negative bacteria.
We summarize their antibacterial and antifungal effects, along with insights into structure-activity relationships that reveal the critical roles of functional groups such as the resorcinol moiety and alkyl side chain.
Mechanistic studies suggest that membrane disruption, metabolic interference, and reactive oxygen species generation contribute to their antimicrobial action. Moreover, we summarize the synergistic potential of cannabinoids when used in combination with conventional antibiotics, highlighting both promising outcomes and notable limitations.
Despite these advances, challenges such as poor solubility, limited in vivo data, and regulatory barriers persist. Addressing these gaps through focused medicinal chemistry and translational research will be essential to harness the full potential of cannabinoids as next-generation antimicrobial agents.”
https://pubmed.ncbi.nlm.nih.gov/41200875/
“Natural and synthetic cannabinoids show activity mainly against Gram-positive bacteria and selected fungi.
Synthetic cannabinoid analogues can enhance potency, selectivity, and pharmacokinetic properties while minimizing psychoactive effects.
Rational modifications to cannabinoid scaffolds, such as the resorcinol ring and alkyl side chain, influence antimicrobial efficacy.
Cannabinoids disrupt microbial membranes, increasing permeability, altering membrane potential, and inducing apoptosis.
Cannabinoids interfere with intracellular metabolic and biosynthetic pathways, impairing energy production and cell wall synthesis.”
https://www.tandfonline.com/doi/full/10.1080/17568919.2025.2580915