This review set out to determine whether cannabis or specific cannabinoid formulations confer clinically meaningful benefit across opioid, alcohol, cocaine, tobacco, and methamphetamine use disorders, classifying studies by design quality and organizing findings by endpoint so that stronger designs and sustained outcomes carried the greatest weight in the conclusions. Against that aim, the central finding is a consistent divergence between symptomatic and sustained therapeutic outcomes of cannabinoid exposure across SUDs. Short-term endpoints (craving, withdrawal severity, and consumption) cluster in the Beneficial direction with comparatively higher tier-weighted totals, while long-term endpoints (retention, relapse, and abstinence) predominantly populate the No Significant Effect category, most strikingly in OUD (Figures 2–4; Table 2). This divergence reflects the inverse relationship between endpoint horizon and evidence tier established in the Results, whereby the most consistent benefits attach to the outcomes assessed by the weakest designs. Together, these findings support a cautious interpretation. Cannabinoid strategies may improve short-horizon symptoms but the current evidence base does not demonstrate that such improvement translates into durable changes in treatment trajectory.

In OUD, where the evidence base is largest, the asymmetry between short-term and long-term SUD endpoints is especially clear, with the heaviest No Significant Effect weights falling on retention and abstinence and exceeding the corresponding symptomatic weights (Table 2). Several methadone and clinic cohorts that verified exposure by urinalysis and tracked administrative retention found no association between cannabis use and illicit opioid use or treatment retention once core clinical covariates were included. In these analyses, cannabis coefficients typically attenuated to null or fluctuated inconsistently after adjustment for factors such as opioid agonist dose, baseline severity, and visit adherence [29, 32, 38, 39, 61, 67, 75, 85, 105]. Consistently, across OUD studies, dose, treatment assignment, and engagement emerged as the dominant drivers of retention and abstinence, and the apparent cannabis signal diminished when these determinants were modeled explicitly [42, 54, 57, 66, 71, 86, 122]. Relapse in OUD demonstrated a similar pattern, with the highest registered tier scores in the No Significant Effect [38, 40, 63, 104, 105, 122] and Harmful/Inferior [33, 53, 77] direction-of-effect categories, with a smaller Beneficial component [58, 70].

AUD and CoUD display related but not identical patterns. In AUD, Beneficial tier weight is concentrated in craving [58, 70, 121, 123], consumption [44, 48, 89, 96, 100], and withdrawal severity [44, 48, 58, 100]. No Significant Effect appears most in craving [109, 119, 120] and consumption [120, 121] within AUD, while harmful signals are scarce [40]. In CoUD, the Beneficial signal again concentrates in short-term SUD endpoints and derives predominantly from qualitative, cross-sectional, and case study designs rather than controlled ones (Table 2), with smaller low-evidence contributions to relapse and abstinence. Qualitative and field investigations consistently describe intentional, post-crack cannabis use to manage the “come down,” reducing agitation, dysphoria, and urges across multiple settings. In mixed methods and longitudinal work, reductions in crack use are sometimes observed in the period after these cannabis substitution episodes rather than during use, suggesting a temporal asymmetry that is mechanistically plausible and clinically testable. This pattern warrants targeted prospective designs that anchor exposure, symptom trajectories, and subsequent consumption temporally to determine whether post-episode mitigation translates into reproducible reductions in stimulant use.

Cannabinoid exposure in CoUD does exhibit a notable non-beneficial footprint. No Significant Effect totals are distributed across all six SUD endpoints [21, 38, 40, 50, 90, 98, 101, 116], while the Harmful/Inferior category includes SUD endpoints in specific observational contexts [65, 80, 95]. Inpatient detox cohorts indicate a correlation between earlier initiation of cannabis and long-duration or heavy use with higher withdrawal scores, more intense craving, and increased re-hospitalizations during CoUD detox, delineating an adverse clinical phenotype within that context [65, 95]. This inpatient signal coexists with the community “come down” narrative, implying that setting, exposure history, and severity shape directionality in CoUD. Future studies should stratify by age of cannabis onset and cumulative exposure to clarify when cannabis use is palliative versus prognostically unfavorable. TUD and MUD contribute far fewer instances overall. Signals trend Beneficial mostly for craving, withdrawal severity, and consumption, with fewer non-beneficial weight recorded [59, 84, 89, 94, 116], but numbers are small and should be read as preliminary.

Taken together, these disorder-specific patterns converge on a single overarching observation. Although cannabinoids may reduce uncomfortable or motivating symptoms in the near term, there is little consistent evidence that such modulation translates into improved treatment course or attainment of sustained non-use. The relative consistency of Beneficial symptom signals suggests that cannabinoids may have a role as adjuncts for short-horizon symptom targets, reducing distressing cravings, mitigating withdrawal experiences, and diminishing overall short-term consumption, at times when such effects can meaningfully support patient engagement or comfort. Such short-term relief from craving, withdrawal, and consumption may itself be valued by patients, even where it does not translate into longer-term treatment benefit. Conversely, the preponderance of No Significant Effect for sustained SUD endpoints, especially in OUD, argues against extrapolating those short-term benefits into assumptions about enduring treatment success. Within the scope of this review, symptom relief is not shown to bridge into sustained therapeutic trajectory or verified non-use at scale.

The tier-weighted framework explains why the short-term/long-term divergence holds even when unweighted counts appear encouraging. By assigning greater weight to randomized and prospective designs, it shows that sustained outcomes are evaluated mainly in higher-tier studies clustering in No Significant Effect, while symptomatic benefits rest disproportionately on lower-tier designs. The few low-tier signals of mild gain in sustained outcomes do not subvert this trend.

This concentration of benefit in the weaker designs is the review’s second principal message, and it carries a specific interpretive risk. Most lower-tier studies are open-label, observational, or qualitative and lack the blinding and placebo control needed to separate a pharmacological effect from expectancy. Cannabinoids are known to produce substantial placebo and expectancy responses. A meta-analysis of double-blind randomized trials in clinical pain found that placebo produced pain reduction comparable to the active cannabinoid [124], and balanced placebo experiments show that the expectancy of having received THC alters subjective and behavioral responses independently of the drug itself [125]. Because craving and withdrawal severity, the endpoints where benefit is most consistent, are largely self-reported and particularly sensitive to expectancy, the symptomatic gains seen in uncontrolled and lower-tier studies may partly reflect these mechanisms rather than a specific cannabinoid action. Caution is, therefore, warranted in attributing even short-term symptom relief to cannabinoids until it is confirmed in adequately powered, placebo-controlled, blinded trials.

A cautious, adjunctive stance appears warranted. The review’s results speak to clinical expectations rather than to the specifics of how cannabinoids should be administered. Where cannabinoids are considered, they are best framed as additions to evidence-based care directed at explicit short-term symptom targets, the only domain in which benefit was observed, and not as a means of improving retention, abstinence, or relapse prevention, for which the present literature shows no consistent effect, particularly in OUD. The non-beneficial and occasionally harmful signals seen in some observational contexts warrant monitoring rather than a presumption of safety. For services and policy makers, these results argue against blanket endorsement while leaving room for methodologically structured exploration where symptom burdens are high and conventional options are constrained.

These findings extend and sharpen themes identified by prior disorder-specific and cannabinoid-specific reviews. In OUD, previous syntheses have reported reductions in craving and anxiety [126], benefit in withdrawal settings on nausea and muscle spasms [127], and modest opioid withdrawal alleviation by dronabinol within a narrow dose range [128]. CBD has been characterized as showing some indication of benefit on opioid craving and anxiety [129], and a cross-SUD review reported beneficial CBD effects in TUD and OUD [130]. Mechanistic syntheses have invoked CBD effects on stress reactivity, sleep, and cue processing to justify adjunctive use [131]. However, when attention shifts from proximal symptoms to sustained outcomes, prior evidence becomes more neutral. Meta-analysis of longitudinal OUD data found no significant cannabis association with mitigating non-medical opioid use [132], and skepticism persists regarding cannabinoid efficacy on stimulant use outcomes [130, 133, 134]. Our tiered synthesis renders those differences visible by disaggregating endpoints and weighting designs within the largest evidence base yet considered, clarifying why mechanistic plausibility should not be conflated with clinical durability.

This review’s principal strengths are its cross-disorder scope and systematic coverage, yielding the largest eligible corpus of human studies on cannabinoid exposure across five SUDs. Careful SUD endpoint mapping upholds the distinction of patient-oriented symptom experience from longer-horizon clinical outcomes and verified use. The tier-weighted scheme privileges controlled designs while incorporating observational and lived-experience evidence, permitting a wide-angle view of efficacy while guarding against overinterpretation of acute laboratory signals.

Several limitations warrant consideration. The corpus remains heterogeneous across exposure definitions, time horizons, outcome definitions, and measurement methods. Many studies rely on self-report for exposure and sometimes for outcomes, complicating dose–response inference. Objective verification, when present, is most common for outcomes such as administrative retention or biochemically verified use, but even then, follow-up durations and analytic choices vary. Observational designs frequently face residual confounding, including time-varying co-use and symptom severity, and selection mechanisms that can make cannabis exposure a marker of underlying risk rather than a modifiable driver of outcomes. Few randomized trials have sufficient size or duration to test whether acute symptom relief mediates clinically meaningful change over the months in which relapse and sustained non-use are decided. Publication bias is plausible, particularly for early-phase symptom results, and may overstate the apparent consistency of Beneficial findings for craving and withdrawal severity. Representativeness is uneven. Opioid medication programs figure prominently in the OUD evidence, while alcohol and cocaine cohorts often come from inpatient or post-discharge settings. Tobacco and methamphetamine domains are comparatively sparse and geographically constrained. In addition, the tier-weighting framework was compiled by the authors for this review and has not been independently validated, so the tier-weighted values should be read as ordinal scaling aids rather than as validated quantitative estimates.

Future research should close three gaps. First, adequately powered, longer-follow-up RCTs that integrate cannabinoids as adjuncts to standard care, with biochemically verified outcomes, time-horizon stratification to map short-term symptom change onto medium-term outcomes, clear specification of product class, dose, route, the cannabidiol (CBD) and tetrahydrocannabinol (THC) ratio (CBD:THC ratio), and systematic monitoring of adverse effects. These trials should be placebo-controlled and blinded, and given the prominence of expectancy in cannabinoid research, future work should also characterize the placebo and expectancy contribution to the SUD-relevant outcomes reported here, across both symptomatic and sustained endpoints, for example, through balanced placebo designs that separate pharmacological from expectancy effects. Second, real-world studies should embrace target-trial emulation, time-varying confounding control, and transparent exposure characterization, acknowledging policy heterogeneity and product variability that plausibly moderate effects. Third, a harmonized endpoint framework, adopted prospectively across disorders, would improve comparability and facilitate the kind of cross-SUD synthesis attempted here.

When disorder, endpoint, and design are considered together, the evidence from 97 studies encompassing 41,954 participants supports a selective conclusion. Cannabinoid strategies most consistently favor symptom relief, targeting craving, withdrawal severity, and reduction of consumption in the acute treatment stage. The firmest conclusions concern OUD, where the eligible literature is by far the most extensive and cannabinoids are predominantly ineffective for enduring clinical outcomes such as retention, relapse, and abstinence. For AUD, CoUD, TUD, and MUD, far fewer studies met eligibility, with TUD and MUD represented by only a handful of instances, so the findings there, in either direction, should be read as preliminary rather than definitive. This disparity reflects the state of the published evidence rather than any restriction of scope, since all studies meeting the prespecified criteria were included. Within the scope and limits of this review, cannabinoids might be considered for short-horizon symptom targets under protocolized conditions, recognizing that even this short-term benefit rests largely on weaker designs, but they should not be assumed to improve long-term treatment trajectory without further evidence. This interpretation integrates the strengths of a tier-aware synthesis with the discipline of endpoint-specific reporting and is offered to inform clinical decision making, service planning, and the design of next-generation trials aligned to sustained therapeutic outcomes.