Category Archives: Addiction

Associations of Low-Level Prenatal Alcohol and Cannabis Exposure With Adolescent Cognitive Trajectories

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“Background: No studies have examined the differential and combined effects of prenatal alcohol and cannabis exposure (PAE/PCE) on longitudinal trajectories of adolescent cognitive development. Further, previous alcohol research is mixed, with some evidence for negative PAE effects on cognition and other studies reporting null or positive associations. This study examined associations between PAE, PCE, and growth trajectories of adolescent cognition in a large, diverse sample.

Methods: N = 11,029 adolescents from the Adolescent Brain Cognitive Development℠ Study completed the NIH Toolbox cognitive battery at baseline (Mage = 9.95), two-year follow-up (Mage = 11.95), and four-year follow-up (Mage = 14.07). Retrospective parent report of PAE and PCE was assessed at baseline. Univariate growth trajectories were estimated for cognitive measures: Pattern Comparison, Picture Sequence Memory, Oral Reading, Flanker Task, and Picture Vocabulary. Cross-product terms for PAE and PCE tested combined use.

Results: Most mothers reported no prenatal alcohol (n = 8257; 74%) or cannabis (n = 10,812; 94%) use. Overall, use was low: across pregnancy, women reporting any alcohol use averaged 33.31 drinks, and those reporting any cannabis use averaged 33.00 use occasions. Before including covariates, there were negative main effects of PCE and positive main effects of PAE on intercepts for all five cognitive domains. There was little evidence for PCE/PAE effects on slopes for cognition. After adding covariates, no negative effects of PCE remained. Small positive PAE effects on intercepts for multiple domains persisted. Cross-product terms for combined exposure were not significant.

Conclusions: Little evidence emerged for negative effects of low PAE, PCE, or combined exposure on adolescents’ cognitive development after accounting for sociodemographic factors. Light drinking in families with social features positively associated with cognitive ability may result in few negative consequences. This study is the first to demonstrate weak evidence for adverse differential and combined low-level PAE and PCE effects on the development of adolescent cognition.”

https://pubmed.ncbi.nlm.nih.gov/41947378

“Little evidence emerged for negative effects of low level prenatal alcohol, cannabis, or combined exposure on adolescents’ cognitive development after accounting for sociodemographic factors.”

https://onlinelibrary.wiley.com/doi/10.1111/acer.70297

Effect of cannabinol, tetrahydrocannabivarin and cannabidiol on voluntary alcohol consumption

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“Aims: Previous studies have demonstrated that the endocannabinoid system plays a significant role in the development of alcohol use disorder (AUD), and CB1 receptor antagonists/inverse agonists show promise as a novel AUD pharmacotherapy. However, these compounds failed in clinical trials due to the severe psychiatric side effects. Non-psychoactive phytocannabinoids may have a better safety profile and could be used as an alternative approach to treat AUD. The aim of this study was to test the potential of three phytocannabinoids in reducing alcohol consumption: CB1 receptor partial agonist cannabinol (CBN), neutral antagonist tetrahydrocannabivarin (THCV) and negative allosteric modulator cannabidiol (CBD).

Methods: Male Wistar rats were subjected to a long-term voluntary alcohol drinking procedure that lasted for several months. Thereafter, rats were given three once daily administrations of CBN, THCV, or CBD. Their side-effect profile was examined by recording changes in water consumption, body weight and locomotor activity. Ultrasonic vocalisations were recorded in alcohol-naïve group-housed rats to monitor if treatment induced discomfort, distress, or other changes in emotional states.

Results: Our data demonstrated that all phytocannabinoids reduced voluntary alcohol consumption; however, the compounds differed in their effectiveness and side-effect profile. Treatment with CBN and THCV reduced alcohol intake and alcohol preference and had a mild sedative effect. CBD had a minor effect on alcohol consumption, did not affect alcohol preference, reduced the locomotor activity and lowered the positive emotional states of rats. None of the compounds caused discomfort or distress.

Conclusions: We conclude that CBN and THCV may have potential in treating AUD.”

https://pubmed.ncbi.nlm.nih.gov/41947574

“Cannabis plants have long been used both medicinally and recreationally, mainly due to the psychoactive compound delta9-tetrahydrocannabinol (THC, a partial agonist of the CB1 receptor). However, the health benefits of these plants may be attributable to over a hundred of other, non-psychoactive compounds or their metabolites, collectively termed phytocannabinoids.”

“In summary, the present study demonstrated that CBN and THCV were more effective in reducing the maintenance of voluntary alcohol consumption and had a better safety profile compared to CBD. The effect of all three phytocannabinoids on alcohol consumption may be related to their action on the CB1 receptor.”

https://academic.oup.com/alcalc/article/61/3/agag019/8607733

Inhibitory effects of Δ8-tetrahydrocannabinol on nicotine metabolism and implications as a smoking cessation agent

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“Tobacco use remains the leading cause of preventable death worldwide. The major metabolic pathway for nicotine, the addictive component in tobacco, is via cytochrome P450 (CYP) 2A6-mediated metabolism to cotinine.

Cannabidiol has been shown to reduce cigarette consumption in vivo and inhibit CYP2A6-mediated nicotine metabolism in vitro. In the present study, Δ-8-tetrahydrocannabinol (Δ8-THC), an isomer of Δ-9-tetrahydrocannabinol, was examined as a potential inhibitor of CYP2A6-mediated nicotine metabolism.

While Δ-9-tetrahydrocannabinol showed no significant inhibition of nicotine metabolism to cotinine, Δ8-THC demonstrated unbound IC50 values of 0.57 ± 0.04 μM in microsomes from recombinant wild-type CYP2A6 overexpressing human embryonic kidney 293 cells and 0.70 ± 0.16 μM in human liver microsomes (HLMs). A similar unbound IC50 value was observed for recombinant CYP2A6∗5 microsomes (0.52 ± 0.17 μM) and was modestly elevated in recombinant CYP2A6∗2 microsomes (1.00 ± 0.12 μM). IC50 shift experiments were consistent across pooled HLM (5.3-fold) and microsomes from liver specimens exhibiting the CYP2A6 (∗2/∗2) and (∗9/∗9) genotypes (6.1- and 4.0-fold, respectively) but were reduced in CYP2A6 (∗35/∗35) microsomes (1.0-fold). Irreversible inhibition kinetics in pooled HLMs by Δ8-THC yielded a kinact value of 0.022 ± 0.001 min-1 and an unbound KI value of 0.232 ± 0.062 μM. Static modeling predicted that oral dosing with 10 mg Δ8-THC increased the nicotine plasma area under the curve by 189%, with further increases observed at 20 mg and 40 mg; interactions were also observed with inhalation doses ≥70 mg.

These findings suggest that, based on CYP2A6 genotype, Δ8-THC could be a candidate for smoking cessation therapy.

SIGNIFICANCE STATEMENT: This study is the first, to the best of our knowledge, to identify Δ-8-tetrahydrocannabinol as a potent and irreversible inhibitor of nicotine metabolism to cotinine. The extent of inhibition is modulated by genetic variation in cytochrome P450 2A6. These findings suggest that further investigations focusing on Δ-8-tetrahydrocannabinol and its potential as a candidate for smoking cessation therapy are warranted.”

https://pubmed.ncbi.nlm.nih.gov/41830876

“In conclusion, the present study is, to our knowledge, the first to demonstrate the irreversible inhibition of nicotine metabolism by Δ8-THC in vitro, highlighting its potential as a smoking cessation agent.”

https://dmd.aspetjournals.org/article/S0090-9556(26)00004-8/fulltext

Alcohol as a Novel Trigger for Cannabis Hyperemesis Syndrome

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“Cannabis hyperemesis syndrome (CHS) is a paradoxical condition occurring in chronic cannabis users, characterized by cyclic nausea, vomiting, and abdominal pain. While the primary trigger is cannabis itself, other precipitants remain poorly defined.

We present the case of a 52-year-old male with recurrent CHS who experienced five distinct hyperemetic episodes, each occurring approximately one week after ingesting a single dose of alcohol. His most recent presentation was complicated by severe, life-threatening hyponatremia requiring intensive care unit management. Diagnostic workup confirmed CHS and excluded other pathologies.

The consistent temporal pattern observed across multiple episodes suggests that a single dose of alcohol may be a novel and specific trigger for CHS. This case highlights a previously underreported precipitant and underscores the syndrome’s potential for severe metabolic complications. Clinicians should consider inquiring about alcohol use in patients with recurrent CHS, as its identification could be pivotal for prevention strategies and patient counseling.”

https://pubmed.ncbi.nlm.nih.gov/41769444

“This case provides critical clinical insights by identifying a single dose of alcohol as a potential novel trigger for CHS, expanding the known spectrum of precipitants. It underscores the serious morbidity of CHS, which can progress to life-threatening complications like severe hyponatremia necessitating intensive care.”

https://www.cureus.com/articles/434462-alcohol-as-a-novel-trigger-for-cannabis-hyperemesis-syndrome#!

“Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A Potential Target to Prevent Alcohol-Induced Neurodegeneration.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC5742761

Potential effects of cannabidiol on formalin-induced inflammatory pain in morphine-dependent rats

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“Chronic morphine exposure leads to tolerance and dependence, complicating pain management and reducing the efficacy of opioid analgesics.

Cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, has been recognized for its anti-inflammatory and analgesic potential.

This study examined the effects of CBD on acute and inflammatory phases of formalin-induced nociception in morphine-dependent and non-dependent rats.

Eighty-four male Wistar rats were divided into the control (non-dependent) and dependent groups. Morphine dependence was induced through an oral escalating-dose regimen in drinking water containing 3% sucrose (to mask bitterness) for 14 days, while controls received only sucrose. CBD (25-200μg/5 μL, ICV) was administered prior to the formalin test. Formalin injection produced a clear biphasic nociceptive response (P < 0.001 in both phases), confirming the model’s validity.

Morphine dependence alone did not significantly affect baseline pain responses (P > 0.05). However, CBD produced a significant, dose-dependent reduction in pain behaviors during both the early (0-5 min) and the late (20-50 min) phases (P<0.001 vs. vehicle). The 100 μg/5 μL and 200 μg/5 μL doses showed the most robust and consistent antinociceptive effect.

CBD produced robust antinociceptive effects in both morphine-treated and non-treated rats, with no statistically significant difference between groups. Open-field results indicated no significant differences in locomotor activity, confirming that the observed analgesia was not related to motor impairment.

These findings demonstrate that CBD effectively attenuates both acute and inflammatory pain. Moreover, it maintains its effectiveness in animals treated with morphine. This highlights its potential as a non-opioid supplementary therapy for managing pain in individuals with opioid dependence.”

https://pubmed.ncbi.nlm.nih.gov/41747636

https://www.sciencedirect.com/science/article/abs/pii/S0022395626001263?via%3Dihub

A CBD-rich hemp extract is superior to CBD alone in reducing relapse to methamphetamine-seeking in rats

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“In preclinical models, the non-intoxicating cannabis component cannabidiol (CBD) reduces relapse to methamphetamine (Meth)-seeking and Meth-induced hyperactivity in rats.

Cannabis products containing multiple cannabinoids (“full spectrum”) may offer greater therapeutic potential than single cannabinoid (“isolate”) products.

However, few studies tested this. This study examined whether a hemp extract (HE) containing multiple cannabinoids might be superior to CBD alone in reducing Meth-induced behavioural sensitisation and relapse, and whether serotonin 1 A receptors (5-HT1A) are involved.

Male Sprague-Dawley rats self-administered either Meth or sucrose via lever press, followed by extinction and reinstatement by Meth injection (1 mg/kg; i.p.) or sucrose access. Rats received vehicle, CBD isolate (80 mg/kg), HE (containing 2.5 mg/kg of CBD and other phytocannabinoids), or HE with CBD added to match the 80 mg/kg amount of the CBD isolate (CBD + HE condition). The 5-HT1A antagonist WAY-100635 was co-administered to assess receptor involvement. Separate rats were tested for conditioned place preference (CPP) to assess possible intrinsic rewarding properties of the cannabinoids. A final group was tested for Meth-induced behavioural sensitisation.

All CBD containing treatments reduced Meth-primed reinstatement, with HE and CBD + HE more effective than CBD isolate.

There was no effect of any treatment on reacquisition of sucrose seeking. WAY-100635 did not block the effects of any treatment. Neither cannabinoid treatment produced CPP. All treatments reduced the expression of Meth-induced sensitised hyperactivity with CBD + HE showing some superiority over CBD or HE alone.

This study suggests that CBD + HE may be more effective than CBD in reducing Meth relapse-like behaviour.”

https://pubmed.ncbi.nlm.nih.gov/41605363

“CBD-rich hemp extract surpasses CBD alone in reducing relapse to Meth-seeking.”

https://www.sciencedirect.com/science/article/pii/S0278584626000254?via%3Dihub

The Exploration of Cannabis Beverage Substitution for Alcohol: A Novel Harm Reduction Strategy

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“Alcohol consumption is associated with nearly 200 health conditions. As cannabis-infused beverages emerge in the legal market, their potential as a substitute for alcohol is of growing interest.

This study investigates whether cannabis beverages may reduce alcohol use.

A total of 438 anonymous adults who used cannabis in the past year completed a survey including cannabis use and alcohol consumption items from the Behavioral Risk Factor Surveillance System (BRFSS). Chi-square and t-tests compared alcohol use between cannabis beverage users and non-users, and before vs. after cannabis beverage initiation.About one-third (33.6%) of respondents used cannabis beverages, typically consuming one per session.

Users were more likely to report substituting cannabis for alcohol (58.6%) than non-users (47.2%). They also reported fewer weekly alcoholic drinks after starting cannabis beverages (M = 3.35) compared to before (M = 7.02), and binge drank less frequently (80.7% reported less than monthly or never, vs. 47.2% before). Those who cited reducing other substance use were more likely to use cannabis beverages (45.8%).

Findings suggest cannabis beverages may support alcohol substitution and reduce alcohol-related harms, offering a promising alternative for individuals seeking to lower alcohol intake.”

https://pubmed.ncbi.nlm.nih.gov/41533430

https://www.tandfonline.com/doi/full/10.1080/02791072.2026.2614506

Cannabidiol reduces oxycodone self-administration while preserving its analgesic efficacy in a rat model of neuropathic pain

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“Prescription opioid misuse is a significant public health concern among individuals with chronic pain. Treating severe pain often requires high doses of opioids, increasing the risk of developing an opioid use disorder.

Cannabidiol (CBD) is a non-intoxicating component of cannabis that has shown therapeutic potential without abuse liability.

This study investigated the effects of CBD on oxycodone self-administration and hyperalgesia in an animal model of chronic neuropathic pain.

Adult male rats were trained to self-administer intravenous oxycodone (0.06 mg/kg/infusion). Subsequently, they underwent chronic constriction injury (CCI) of the sciatic nerve or received sham surgery. Paw withdrawal latency was measured using the Hargreaves test as an indicator of thermal pain sensitivity. CBD (0, 1, 3, and 10 mg/kg, IP) was administered before the self-administration sessions, and pain testing was conducted afterward. The rats acquired oxycodone self-administration, as indicated by more active than inactive lever presses. CCI surgery decreased the paw withdrawal latency, confirming the induction of neuropathic pain. CCI alone did not affect oxycodone self-administration, suggesting that neuropathic pain does not substantially influence opioid intake at the dose tested.

Treatment with CBD reduced oxycodone self-administration in both the sham and CCI rats. Oxycodone self-administration in the CCI rats reversed the CCI-induced decrease in paw withdrawal latency. However, CBD did not affect the antinociceptive effect of oxycodone in CCI rats.

Taken together, these findings demonstrate that CBD reduces oxycodone self-administration without affecting the antinociceptive effects of oxycodone in neuropathic pain.

This study supports the potential of CBD to reduce opioid use and misuse, regardless of pain status.”

https://pubmed.ncbi.nlm.nih.gov/41521216

https://www.nature.com/articles/s41598-025-31828-y

Effect of patient marijuana use on perioperative opioid requirements

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“The effect of chronic marijuana use on patients is unknown, including in the surgical setting. Marijuana produces many effects on the body, which should be considered when providing medical care.

Chronic marijuana use may affect surgical opioid requirements. To explore this possibility, an observational study was completed by conducting a retrospective chart review of patients who underwent surgery with general anesthesia.

Patients were identified in the electronic medical record via self-reporting as marijuana users (users) or nonmarijuana users (nonusers). Users and nonusers were case-matched based on age, gender, weight, and procedure. After case matching, 570 patients’ charts were analyzed, and intraoperative opioid, intraoperative propofol, and post-anesthesia care unit opioid requirements were compared.

Marijuana users required less intraoperative opioids (mean [standard deviation (SD)] 27.2 [20.5] morphine milligram equivalents [MMEs]) compared to those who were marijuana nonusers (31.3 [22.1] MME).

These results show a statistically significant difference in the intraoperative opioid requirement between case-matched users and nonusers (p = 0.02), with p = 0.013 after statistical adjustment for racial differences between the marijuana user and nonuser cohorts. Users and nonusers required similar amounts of intraoperative propofol (242.2 [220.2] and 257.8 [250.9], respectively) and post-operative opioids (7.3 [6.0] and 8.0 [9.0], respectively). The differences in intraoperative propofol and post-operative opioid requirements were not different statistically with p-values of 0.43 and 0.31, respectively.

Based on this study population, marijuana users required less intraoperative opioids when compared to case-matched marijuana nonusers, with no difference in intraoperative propofol or post-operative opioid requirements.

Perspective: Typical preoperative screening includes queries about patient substance use including marijuana, but details such as frequency and length of use are infrequently asked. The addition of these details to the assessment may provide improved understanding of a patient’s surgical opioid requirements.”

https://pubmed.ncbi.nlm.nih.gov/41123263

https://wmpllc.org/ojs/index.php/jom/article/view/3918

Medical Cannabis and Opioid Receipt Among Adults With Chronic Pain

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“Question  Is participation in the New York State (NYS) medical cannabis program associated with reduced prescription opioid receipt among adults with chronic pain?

Findings  In this cohort study of 204 adults with chronic pain, participation in the NYS medical cannabis program, defined as monthly dispensation of medical cannabis reported by the dispensary pharmacist, was associated with significantly reduced prescription opioid receipt.

Meaning  These findings suggest that participation in a pharmacist-directed medical cannabis program may help reduce prescription opioid receipt among adults with chronic pain.

Abstract

Importance  Medical cannabis is increasingly considered a substitute for prescription opioid medications for chronic pain, driven by the urgent need for opioid alternatives to combat the ongoing epidemic.

Objective  To determine the association between participation in the New York State (NYS) medical cannabis program and prescription opioid receipt among adults with chronic pain.

Design, Setting, and Participants  This cohort study used data from the NYS Prescription Monitoring Program (PMP) from September 2018 through July 2023. Adults prescribed opioids for chronic pain who were newly certified for medical cannabis use in NYS were recruited from a large academic medical center and nearby medical cannabis dispensaries in the Bronx, New York. Monthly dispensation of medical cannabis to study participants was monitored for 18 months. Data analyses were performed from February 3, 2025, to July 15, 2025.

Exposure  Portion of days covered each month by pharmacist report of dispensed medical cannabis.

Main Outcomes and Measures  Prescription opioid receipt, defined as NYS PMP-reported prescription monthly opioid dispensation (mean daily dose in morphine milliequivalents [MME]), was assessed with marginal structural models adjusted for time-invariant and time-varying confounders, including self-reported unregulated cannabis use. Nonprescribed opioid use was also assessed during the study period.

Results  Among 204 participants, the mean (SD) age at baseline was 56.8 (12.8) years, and 113 (55.4%) were female. At baseline, participants’ mean (SD) pain severity score was 6.6 (1.8) out of 10, and mean (SD) pain interference score was 6.8 (1.9) out of 10. Baseline mean (SD) daily MME was 73.3 (133.0). During the 18-month follow-up period, participants’ mean (SD) daily MME decreased to 57.4 (127.8). This reduction in mean daily MME was associated with the monthly portion of days covered with medical cannabis; compared with no medical cannabis dispensed, participants dispensed a 30-day supply of medical cannabis were exposed to 3.53 fewer MME per day (β = −3.53; 95% CI, −6.68 to −0.04; P = .03).

Conclusions and Relevance  In this cohort study, participation in NYS’s medical cannabis program was associated with reduced prescription opioid receipt during 18 months of prospective follow-up, accounting for unregulated cannabis use.”

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2842414