Category Archives: Addiction

Combination of Cannabidiol and Low-Dose Buprenorphine Suggests Synergistic Analgesia and Attenuates Buprenorphine-Induced Respiratory Depression

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“Introduction: As opioid-related drug overdoses remain a public health crisis, there is a critical need for innovative approaches to developing safer analgesics with improved safety profiles. BDH-001 is a fixed-dose combination of low-dose buprenorphine (BUP) and cannabidiol (CBD) being developed as a safer analgesic than currently available opioids. The purpose of this study was to examine the analgesic and opioid-sparing effects of BDH-001 and to complete an in vivo safety assessment in rats. 

Methods: Analgesic effect of BDH-001 was assessed using the chronic constriction injury model of chronic neuropathic pain with pain threshold assessed via Von Frey testing. Drug-drug interaction effects on pharmacokinetic (PK) parameters were assessed in a single dose PK study in rodents. The effects on respiratory depression were also assessed and confirmed in two separate rodent studies performing blood gas analysis and measuring O2 saturation. 

Results: BDH-001 (combination of subanalgesic BUP dose and CBD) resulted in statistically significant increases in pain threshold compared to saline (p < 0.001), CBD alone (p < 0.01), and BUP alone (p < 0.05). The half-life of BUP was significantly shorter in the presence of CBD compared to BUP alone (p = 0.008), with no significant changes in any other BUP pharmacokinetic parameter assessed. CBD was found to attenuate BUP-induced respiratory depression in rats when assessing blood gases (p < 0.05) and O2 saturation (p < 0.05) over several time bins. 

Conclusions: Data obtained in the present study indicate the addition of CBD to BUP was opioid-sparing and attenuated BUP- but not morphine-induced respiratory depression. There was no evidence these findings were the result of a PK interaction. Results support the hypothesis that BDH-001, a fixed-dose combination of BUP and CBD, may provide effective analgesia with a more favorable safety profile.”

https://pubmed.ncbi.nlm.nih.gov/40468945/

https://www.liebertpub.com/doi/10.1089/can.2025.0004

“Buprenorphine is a medication that plays a crucial role in treating opioid use disorder (OUD), also known as opioid addiction. It works by partially activating the same receptors in the brain as opioids, helping to reduce withdrawal symptoms and cravings without producing the intense euphoria or dangerous side effects associated with full opioid agonists like heroin or fentanyl.”

Cannabidiol dose dependently reduces alcohol intake in mice via a non-5-HT1A receptor mechanism: Exploration of other potential receptor targets

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“Background and purpose: Binge drinking is a risky pattern of alcohol intake and a major predictor of alcohol use disorder (AUD). Current AUD medications have limited efficacy and poor patient compliance, calling for more effective therapeutics. Cannabidiol (CBD), a non-intoxicating component of cannabis, has emerged as a potential novel therapeutic. However, receptor mechanisms in CBD’s alcohol-related effects have not been investigated comprehensively.

Experimental approach: Using the murine drinking-in-the-dark model of binge drinking, our research aimed to confirm a reduction of alcohol consumption with CBD (7.5, 15, 30, 60, 120 mg kg-1) in male and female mice. Behavioural pharmacological approaches were used to explore CBD interactions with identified target mechanisms: serotonin-1A receptor (5-HT1AR) and peroxisome proliferator-activated receptor-gamma (PPARɣ), and the novel targets, chemokine receptor type-4 (CXCR4) and neuropeptide S receptor (NPSR).

Key results: Acute CBD dose dependently suppressed binge-like drinking and blood ethanol concentration. The effect was not driven by locomotor impairments and was maintained across sub-chronic treatment. Blockade of 5-HT1AR and PPARɣ had no impact on CBD’s reduction of alcohol consumption. Co-administration of subthreshold CBD doses and a NPSR antagonist implicated NPSR blockade as a potential mechanism contributing to CBD’s effect, whereas co-administration of CBD and a CXCR4 antagonist suggested CXCR4 was not involved. However, the potent and selective CXCR4 antagonist AMD3100 reduced ethanol consumption.

Conclusions and implications: CBD represents a promising candidate to reduce voluntary alcohol consumption. Mechanisms driving CBD’s alcohol-related effects remain unclear and may involve polypharmacology, including actions at the NPSR identified in the present study.”

https://pubmed.ncbi.nlm.nih.gov/40432283/

“These experiments consistently showed a dose-dependent suppression of alcohol consumption by CBD.”

https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.70070

Effects of legal access versus illegal market cannabis on use and mental health: A randomized controlled trial

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“Aims: We measured the effects of public health-oriented cannabis access compared with the illegal market on cannabis use and related mental health outcomes in adult cannabis users.

Design: This was a two-arm, parallel group, open-label, randomized controlled trial. Follow-up outcome measurement took place after 6 months.

Setting: The study was conducted in Basel-Stadt, Switzerland.

Participants: A total of 378 adult (aged ≥18 years) cannabis users were enrolled and randomized between August 2022 and March 2023, although only 374 users who completed baseline measures could be included.

Intervention and comparator: Participants were randomly assigned to the intervention group with public health-oriented recreational cannabis access in pharmacies (regulated cannabis products, safer use information, voluntary counseling, no advertisement; 189/188) or the illegal market control group (continued illicit cannabis sourcing; 189/186).

Measurements: The primary outcome was self-reported severity of cannabis misuse after 6 months, as measured by the Cannabis Use Disorders Identification Test – Revised (range 0-32). Secondary outcomes involved depressive, anxiety, and psychotic symptoms, cannabis consumption amount, alcohol, and drug use.

Findings: Ten participants were not followed (2.7%). Primary analysis included those with complete data (182 vs. 182). There was some evidence of a difference in cannabis misuse between the legal cannabis intervention group (mean [M] = 10.1) and the illegal market control group (M = 10.9; β = -0.69, 95% confidence interval [CI] = -1.4 to 0.0, P = 0.052). These results were supported by an intention-to-treat multiple imputation analysis (n = 374). Additional sub-group analysis by whether the participant used other drugs or not suggested that any reduction in cannabis misuse was confined to those in the legal cannabis intervention group who used other drugs (PInteraction < 0.001). We found no statistically significant changes in any of the secondary outcomes.

Conclusions: Public health-oriented recreational cannabis access may decrease cannabis use and cannabis-related harms, especially among those using other drugs.”

https://pubmed.ncbi.nlm.nih.gov/40289676/

“Our results indicate that public health-oriented RCL could be an effective policy model to make cannabis safer without increasing cannabis use and cannabis-related harms.”

https://onlinelibrary.wiley.com/doi/10.1111/add.70080

“Cannabis study finds legalization reduces problematic consumption, especially among those using other drugs”

https://medicalxpress.com/news/2025-05-cannabis-legalization-problematic-consumption-drugs.html

“Researchers uncover causal evidence that cannabis legalization reduces problematic consumption”

Researchers uncover causal evidence that cannabis legalization reduces problematic consumption

“Legal Cannabis Linked to Less Problematic Use, Better Mental Health”

Legal Cannabis Linked to Less Problematic Use, Better Mental Health

Cost-Effectiveness of Medical Cannabis Versus Opioids for Chronic Noncancer Pain

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“Background: Chronic noncancer pain (CNCP) affects one in five adults and is commonly managed with long-term opioid therapy. Concerns regarding rare but catastrophic harms associated with opioids, including overdose and death, have generated interest in alternatives including cannabis; however, the comparative cost-effectiveness of these management options is uncertain. 

Methods: We used findings from a network meta-analysis of 90 randomized trials to develop a 1-year microsimulation model to compare costs and quality-adjusted life years (QALY) between oral medical cannabis and opioids for CNCP. We used a publicly funded health care payer perspective for our analyses and obtained cost and utility data from publicly available sources. All costs are reported in 2023 Canadian dollars. All analyses were probabilistic, and we conducted sensitivity and scenario analyses to assess robustness. 

Results: Total mean annual cost per patient was $1,980 for oral medical cannabis and $1,851 for opioids, a difference of $129 (95% confidence interval [CI]: -$723 to $525). Mean QALYs were 0.582 for both oral medical cannabis and opioids (95% CI: -0.007 to 0.015). Cost-effectiveness acceptability curves showed that oral medical cannabis was cost-effective in 31% of iterations at willingness-to-pay thresholds up to $50,000/QALY gained.

Use of opioids is associated with nonfatal and fatal overdose, whereas medical cannabis is not. 

Discussion: Our findings suggest that medical cannabis as an alternative to opioids for chronic pain may confer similar, but modest, benefits to patients, and reduce the risk of opioid overdose without substantially increasing costs.”

https://pubmed.ncbi.nlm.nih.gov/40304409/

https://www.liebertpub.com/doi/10.1089/can.2024.0120

Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model

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“Background: Schizophrenia (SCZ) has limited treatment options, often with significant side effects. Cannabidiol (CBD), a non-euphoric phytocannabinoid, has shown potential as a novel therapeutic option in SCZ due to antipsychotic-like, anti-inflammatory, and antioxidant properties. We compared the therapeutic effects of CBD and risperidone (RISP) in a rat model of SCZ induced by sub-chronic ketamine (KET), focusing on inflammatory and oxidative stress, and behavioral phenotypes.

Methods: Rats were pre-treated with KET or saline (SAL) for 10 days followed by CBD or RISP for 8 days. Locomotion, anxiety- and anhedonia-like behavior, and recognition memory were assessed. Oxidative damage as measured by protein carbonyls, thiobarbituric acid reactive substances, and catalase activity, and the inflammation markers myeloperoxidase (MPO) activity and nitrite/nitrate (N/N) concentration ratio were assessed in the prefrontal cortex (PFC), hypothalamus (HYP), hippocampus (HPC), and striatum, brain areas relevant to SCZ.

Results: CBD restored the KET-induced decreased rearing behavior in the OFT, while RISP further decreased rearing. RISP treatment in control rats decreased rearing and elicited an anhedonic-like phenotype, while CBD did not. CBD, but not RISP restored the KET-induced increased levels of MPO activity in the PFC and the striatum, and protein carbonyls in the HPC. Post-KET treatment with RISP but not CBD decreased protein carbonyls in the PFC, and decreased the N/N concentration ratio in the HYP.

Conclusion: CBD restored the KET-induced decrease in rearing behavior without inducing an anhedonic-like phenotype as observed with RISP. CBD, and to a lesser extent RISP restored the oxidative stress and neuroinflammation elicited by KET in the striatum, HPC, and PFC. These findings support the possibility that the antipsychotic effects of CBD might be mediated by its antioxidant and anti-inflammatory effects.”

https://pubmed.ncbi.nlm.nih.gov/40132281/

https://www.sciencedirect.com/science/article/abs/pii/S0920996425000908?via%3Dihub

Cannabis use and illicit opioid cessation among people who use drugs living with chronic pain

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“Introduction: Amidst the opioid overdose crisis, there is interest in cannabis use for pain management and harm reduction. We investigated the relationship between cannabis use and cessation of unregulated opioid use among people who use drugs (PWUD) living with chronic pain.

Method: Data for analyses were collected from three prospective cohort studies in Vancouver, Canada. All cohort participants who completed at least two study visits and reported both pain and unregulated opioid use in the past 6 months were included in the present study. We analysed the association between cannabis use frequency and opioid cessation rates using extended Cox regression models with time-updated covariates.

Results: Between June 2014 and May 2022, 2340 PWUD were initially recruited and of those 1242 PWUD reported chronic pain, use of unregulated opioids and completed at least two follow-up visits. Of these 1242 participants, 764 experienced a cessation event over 1038.2 person-years resulting in a cessation rate of 28.5 per 100 person-years (95% confidence interval [CI] 25.4-31.9). Daily cannabis use was positively associated with opioid cessation (adjusted hazard ratio 1.40, 95% CI 1.08-1.81; p = 0.011). In the sex-stratified sub-analyses, daily cannabis use was significantly associated with increased rates of opioid cessation among males (adjusted hazard ratio 1.50, 95% CI 1.09-2.08; p = 0.014).

Discussion and conclusions: Participants reporting daily cannabis use exhibited higher rates of cessation compared to less frequent users or non-users. Observed sex-specific differences in cannabis use and opioid cessation suggest potential differences in cannabis use behaviours and effects. Our findings add to the growing evidence supporting the potential benefits of cannabis use among PWUD, underlining the need for further research.”

https://pubmed.ncbi.nlm.nih.gov/40011075/

Recreational Cannabis Laws and Fills of Pain Prescriptions in the Privately Insured

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“Objective: Almost half of U.S. states have passed recreational cannabis laws as of May 2024. While considerable evidence to date indicates cannabis may be a substitute for prescription opioids in the treatment of pain, it remains unclear if patients are treating pain with cannabis alone or concomitantly with other medications.

Method: Using data from a national sample of commercially insured adults, we examine the effect of recreational cannabis legalization (through two sequential policies) on prescribing of opioids, NSAIDS, and other pain medications by implementing synthetic control estimations and constructing case-study level counterfactuals for the years 2007-2020.

Results: Overall, we find recreational cannabis legalization is associated with a decrease in opioid fills among commercially insured adults in the U.S., and we find evidence of a compositional change in prescriptions of pain medications more broadly. Specifically, we find marginally significant increases in prescribing of non-opioid pain medications after recreational cannabis becomes legal in some states. Once recreational cannabis dispensaries open, we find statistically significant decreases in the rate of opioid prescriptions (13% reduction from baseline, p < .05) and marginally significant decreases in the average daily supply of opioids (6.3% decrease, p < .10) and number of opioid prescriptions per patient (3.5% decrease, p < .10).

Conclusions: These results suggest that substitution of cannabis for traditional pain medications increases as the availability of recreational cannabis increases. There appears to be a small shift once recreational cannabis becomes legal, but we see stronger results once users can purchase cannabis at recreational dispensaries. The decrease in opioids and marginal increase in non-opioid pain medication may reflect patients substituting opioids with cannabis and non-opioid pain medications, either separately or concomitantly. Reductions in opioid prescription fills stemming from recreational cannabis legalization may prevent exposure to opioids in patients with pain and lead to decreases in the number of new opioid users, rates of opioid use disorder, and related harms.”

https://pubmed.ncbi.nlm.nih.gov/39968486/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/268

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

Cannabidiol interactions with oxycodone analgesia in an operant orofacial cutaneous thermal pain assay following oral administration in rats

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“Previous studies have driven the notion that the cannabis constituent cannabidiol could be an effective adjunct to opioid administration for managing pain.

Most of these studies have used experimental rodents with routes of administration, such as subcutaneous and intraperitoneal, that do not correspond with the routes used in clinical practice. In response to this, we tested the ability of cannabidiol co-administration to augment opioid analgesia via the more clinically-relevant oral route of administration.

To this end, male and female rats were orally gavaged with cannabidiol (25 mg/kg), oxycodone (1.4 mg/kg), or a combination of both, after which they were tested in an operant thermal orofacial pain assay in which they voluntarily exposed their faces to cutaneous thermal pain to receive a palatable reward.

All three drug conditions produced analgesic effects of varying degrees, being most profound in the combination group where a statistically significant enhancement over oxycodone-induced analgesia alone was evident. Additionally, oxycodone administration decreased lick frequencies – a measure of motor coordination of rhythmic movements – which too was magnified by co-administration of cannabidiol.

Together these studies provide further support of an ability of cannabidiol to augment opioid effects, particularly analgesia, when administered by a route relevant to human pain management. As such, they encourage the notion that cannabidiol could find utility as an opioid-sparing approach to treating pain.”

https://pubmed.ncbi.nlm.nih.gov/39914591/

“Cannabidiol is an orally active constituent of the cannabis plant”

“Cannabidiol potentiates opioid analgesia in an operant orofacial pain assay in rats”

“Cannabidiol as an opioid-sparing approach to treating pain is worthy of more study”

https://www.sciencedirect.com/science/article/abs/pii/S0091305725000152?via%3Dihub

Cannabidiol alters psychophysiological, craving and anxiety responses in an alcohol cue reactivity task: A cross-over randomized controlled trial

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“Background: Preclinical studies have demonstrated that cannabidiol (CBD) reduces alcohol-seeking behaviors and may have potential for managing alcohol use disorder (AUD). In this study, we examined the effects of CBD versus placebo on (i) psychophysiological, craving and anxiety responses to alcohol and appetitive cues; (ii) tolerability measures including cognitive functioning.

Methods: Twenty-two non-treatment-seeking individuals with AUD (DSM-5) participated in a cross-over, double-blind, randomized trial, receiving either 800 mg of CBD or matched placebo over 3 days. A laboratory alcohol cue reactivity task with appetitive control (juice) and alcohol exposures, and subsequent recovery periods to examine regulation of cue-elicited responses after cue-offset (recovery) was completed, with psychophysiological indices of autonomic nervous system activity (skin conductance, high-frequency heart rate variability [HF-HRV]) and self-reported measures (alcohol craving and anxiety). Self-reported scales of sedation and neuropsychological executive function tasks were also completed.

Results: CBD sessions were significantly associated with elevated parasympathetic nervous system (PNS) activity across the task, as indicated by increased HF-HRV. Reductions in self-reported anxiety during cue exposure stages compared to placebo sessions were also evidenced. Reductions in self-reported alcohol craving after cue exposure were seen during CBD sessions only. There were no significant differences between CBD and placebo on executive functioning performance.

Conclusions: In a short-term regimen, CBD appears to modulate PNS activity, reduce cue-elicited anxiety during cue exposure and reduce alcohol craving after cue exposure while not significantly impairing cognition. Large, parallel clinical trials with longer term regimens are now needed to determine the therapeutic potential of CBD in the management of AUD.”

https://pubmed.ncbi.nlm.nih.gov/39891614/

https://onlinelibrary.wiley.com/doi/10.1111/acer.15514