Low-Dose Naltrexone and Cannabis: The Full Interaction Profile

What low-dose naltrexone actually is

No FDA-approved low-dose naltrexone product exists. LDN means naltrexone at 0.5 to 6 mg a day, most often 4.5 mg, used off-label for conditions such as fibromyalgia, multiple sclerosis, Crohn's disease and long COVID, and supplied mainly through compounding pharmacies [4]. FDA states that compounded drugs are not FDA-approved and that it does not verify their safety, effectiveness or quality before they are marketed [5]. A 2026 narrative review calls the 4.5 mg dose 'empirically derived rather than evidence-based' [4].

The tablet label covers 50 mg oral naltrexone [1], and the Vivitrol label covers a 380 mg extended-release injection [2]. Neither gives dose-specific guidance for LDN [1][2][4]. So a statement about 'the naltrexone label' describes a 50 mg tablet or a 380 mg injection, not a compounded 4.5 mg capsule. HealthRX.com offers low-dose naltrexone by prescription.

What the closest study found

Haney and colleagues ran a double-blind, placebo-controlled human laboratory study in non-treatment-seeking daily cannabis smokers: 51 people randomized to naltrexone 50 mg (23 participants) or placebo (28) for 16 days, with 10 laboratory sessions before, during and after medication [3].

Compared with placebo, naltrexone reduced both active cannabis self-administration and the 'good effect' rating from cannabis. The placebo group had 7.6 times the odds of self-administering active cannabis (95% CI 1.1 to 51.8) [3]. Naltrexone also had its own effects: lower ratings of friendliness, lower food intake, lower systolic blood pressure, and more spontaneous reports of stomach upset and headache, with dropout comparable between groups [3].

Two limits matter. The dose was 50 mg, not an LDN dose, so the study does not say what 4.5 mg would do. And it measured what naltrexone did to cannabis, not what cannabis does to naltrexone.

Does cannabis blunt LDN?

In the laboratory study described above, the effect ran from naltrexone to cannabis: naltrexone weakened cannabis reward [3]. Nothing in that study addresses the reverse. LDN's proposed mechanisms (TLR4 antagonism on microglia, brief opioid-receptor blockade with compensatory upregulation of endogenous opioid signalling, and opioid growth factor receptor effects) remain 'largely theoretical and speculative' according to the 2026 review [4][6].

Naltrexone is a pure opioid antagonist that blocks opioid effects by competitive binding at opioid receptors, and it precipitates withdrawal in people physically dependent on opioids [1]. Cannabis is not an opioid, so the opioid-related rules in the labels are about a different class of drug.

Cannabis in a large naltrexone trial

X:BOT randomized 570 adults with opioid use disorder to extended-release naltrexone (283 participants) or buprenorphine-naloxone (287) for 24 weeks [7]. A secondary analysis looked at cannabis use: participants assigned buprenorphine-naloxone were 39% less likely to use cannabis than those assigned naltrexone across all timepoints (p=0.0499), and no significant mediation was found between treatment assignment and cannabis or opioid outcomes [8].

That trial used the monthly injection in people with opioid use disorder. It does not describe people taking compounded LDN, and it does not test cannabis as a cause of anything.

What the labels address

The naltrexone tablet and Vivitrol labels are built around opioid blockade. Both list as contraindications: patients receiving opioid analgesics, patients currently dependent on opioids (including methadone or buprenorphine maintenance), patients in acute opioid withdrawal, anyone who failed a naloxone challenge test or has a positive urine screen for opioids, and anyone with a history of hypersensitivity to the product [1][2]. Cannabis is not named in those lists [1].

• The tablet label recommends an opioid-free interval of at least 7 to 10 days before starting, and says people moving from buprenorphine or methadone may remain vulnerable to precipitated withdrawal for as long as 2 weeks [1].
• The tablet label says precipitated withdrawal in an opioid-dependent person can be severe enough to require hospitalization; symptoms usually appeared within 5 minutes of ingestion and lasted up to 48 hours [1].
• The tablet label says disulfiram is not ordinarily combined with naltrexone because both are potentially hepatotoxic, and that lethargy and somnolence have been reported with naltrexone plus thioridazine [1].
• Both labels say to strongly consider an opioid overdose reversal agent (naloxone or nalmefene) at the start of treatment and at each renewal or injection, because opioid tolerance is lower after treatment ends, at the end of a dosing interval, or after a missed dose [1][2].
• Neither the current tablet label nor the current Vivitrol label has a boxed warning; hepatotoxicity is in the warnings section [1][2].

None of these are cannabis interactions. They are the safety topics the labels actually cover.

Bottom line

A laboratory study found that 50 mg oral naltrexone reduced cannabis self-administration and its 'good effect' rating [3]. A separate analysis examined cannabis use among people assigned extended-release naltrexone injections for opioid use disorder [8]. Neither tested LDN. LDN is used off-label and supplied mainly through compounding pharmacies [4], and compounded drugs are not FDA-approved [5]. The label cautions centre on opioids rather than cannabis [1], and LDN's commonly reported effects are insomnia, vivid dreams, nausea and dizziness [4].