Examining the scientific evidence behind CBD and THC as potential treatments for various substance use disorders
Substance use disorders represent one of the most significant public health challenges of our time, affecting millions globally and creating a staggering economic burden. With limited treatment options and high relapse rates, researchers have been urgently seeking alternative therapeutic approaches.
An umbrella review published in 2025 in the journal Addiction set out to answer this question by analyzing all available systematic reviews on CBD alone or in combination with Δ-9-tetrahydrocannabinol (THC) for managing substance use disorders 1 2 .
Substance use disorders affect millions worldwide with limited effective treatments
Non-intoxicating cannabis compound being studied as alternative treatment
2025 umbrella review analyzed all available systematic reviews
To understand why researchers are investigating cannabinoids for substance use disorders, we first need to consider how addiction affects the brain and how these compounds might intervene.
Addiction is increasingly understood as a chronic brain disorder characterized by compulsive substance use despite harmful consequences. The key player is the mesolimbic dopamine pathway, often called the brain's reward circuit 3 .
This system, which includes the ventral tegmental area and nucleus accumbens, normally reinforces behaviors essential for survival, like eating and socializing, by releasing dopamine—a neurotransmitter associated with pleasure and motivation.
Drugs of abuse—whether alcohol, opioids, or nicotine—hijack this system, causing unnaturally large surges of dopamine that create powerful reinforcement for continued use.
The endocannabinoid system serves as a crucial modulator of brain activity. This system includes cannabinoid receptors (CB1 and CB2) scattered throughout the brain and body, plus naturally occurring cannabinoids our bodies produce 3 .
Think of it as a fine-tuning mechanism for neurotransmitter activity—it helps regulate everything from mood and memory to pain perception and reward.
CB1 receptors are particularly abundant in brain regions central to addiction, including the prefrontal cortex (involved in decision-making) and the nucleus accumbens (central to reward processing) 3 .
THC, the psychoactive component of cannabis, binds directly to CB1 receptors, mimicking our natural cannabinoids and producing the "high" associated with marijuana. CBD, in contrast, has a more complex mechanism of action—it doesn't bind strongly to CB1 receptors but influences the system in other ways, potentially modulating the effects of THC and increasing levels of our natural cannabinoids 3 .
In 2025, a comprehensive umbrella review sought to resolve the conflicting evidence about CBD's efficacy for substance use disorders. Umbrella reviews represent the highest level of evidence synthesis—they don't examine individual studies but instead analyze multiple systematic reviews and meta-analyses to provide a broad perspective on what the scientific literature collectively demonstrates.
This ambitious review analyzed 22 systematic reviews (5 of which included meta-analyses) covering randomized controlled trials that tested CBD alone or in combination with THC for various substance use disorders 1 2 . The findings provided crucial insights into what works—and what doesn't.
| Substance | CBD Alone | CBD+THC Combination | Key Findings |
|---|---|---|---|
| Cannabis | Limited efficacy | Positive effects | Nabiximols (CBD+THC) reduced withdrawal and craving |
| Tobacco | Inconclusive | Not tested | Evidence insufficient to draw conclusions |
| Alcohol | Inconclusive | Not tested | Mixed results across studies |
| Opioids | Inconclusive | Not tested | Limited evidence available |
| Psychostimulants | Inconclusive | Not tested | Insufficient research to date |
The researchers offered several potential explanations for CBD's limited performance as a standalone treatment:
The quality of many systematic reviews was variable, with only a minority conducting meta-analyses that provide more rigorous statistical conclusions.
The underlying clinical trials varied considerably in their methodologies, CBD formulations, dosages, and treatment durations, making consistent effects difficult to detect.
It's possible that CBD's effects are simply too modest to demonstrate clear benefits given the current research methodologies.
To better understand what cannabinoid research looks like in practice, let's examine a specific clinical trial that investigated CBD for alcohol use disorder. A 2025 study published in Frontiers in Psychiatry provides an excellent case study of the promises and challenges in this field 4 .
This randomized, double-blind, placebo-controlled trial—the gold standard in clinical research—aimed to assess both the safety and potential efficacy of two types of CBD products for adults with moderate to severe alcohol use disorder 4 .
Adults with moderate to severe alcohol use disorder
Plus 8 weeks of follow-up observation
Full-spectrum CBD, broad-spectrum CBD, and placebo
| Outcome Measure | Full-Spectrum CBD | Broad-Spectrum CBD | Placebo |
|---|---|---|---|
| Alcohol Craving | Significant reduction | Minimal reduction | Minimal reduction |
| Drinks per Drinking Day | No significant reduction | No significant reduction | No significant reduction |
| AUD Symptoms | Greater reduction | Minimal reduction | Minimal reduction |
| Safety Profile | Well-tolerated | Well-tolerated | Well-tolerated |
As a pilot study with a relatively small sample size, these findings should be considered preliminary. The researchers appropriately noted that "future studies with larger sample sizes will be necessary to replicate and extend these findings" 4 .
Conducting rigorous research on cannabinoids requires specific tools and methodologies. Here's a look at the essential components of the "scientist's toolkit" in this field:
| Tool | Function | Example/Notes |
|---|---|---|
| Pharmaceutical-grade CBD | Ensures consistent purity and dosage | Epidiolex®; used as reference standard |
| Placebo Control | Isolates specific effects from psychological expectations | Matched in appearance and taste to active product |
| Randomization | Reduces selection bias | Participants randomly assigned to treatment groups |
| Blinding | Prevents bias in reporting outcomes | Double-blind design where neither participants nor researchers know who receives active treatment |
| Validated Assessment Tools | Measures substance use, craving, withdrawal | Timeline Followback Method for alcohol consumption; Penn Alcohol Craving Scale |
| Biomarker Analysis | Objective measures of compliance and safety | Blood samples to measure cannabinoid levels and liver enzymes |
The randomized controlled trial design represents the gold standard because it minimizes the numerous biases that can affect study outcomes.
The use of pharmaceutical-grade cannabinoids addresses the problem of product variability that complicates interpretation of studies using commercially available products 9 .
The recent umbrella review on cannabinoids for substance use disorders provides a sobering counterpoint to the enthusiasm that often surrounds CBD in popular media. The conclusion that "CBD monotherapy does not appear to be efficacious" for substance use disorders reminds us that promising theoretical mechanisms don't always translate to clinical benefits 1 2 .
The combination of CBD and THC in nabiximols shows promise for cannabis withdrawal and craving 1 .
The alcohol use disorder trial suggests that full-spectrum CBD with trace THC might reduce craving even when it doesn't reduce consumption 4 .
References to be added manually here