Opioids such as morphine, codeine and methadone are powerful pain relievers, but they carry well-known risks, including tolerance, dependence and overdose. For people who develop opioid use disorder, long-term pain can make recovery much harder. Researchers are therefore exploring whether non-opioid options could help manage pain without adding to opioid-related harm.
A research team in the United States recently tested one such candidate, cannabidiol (CBD). They aimed to evaluate its effects on pain, craving, and cognition among patients with opioid use disorder (OUD) and chronic pain receiving methadone. Their findings, published in the journal Neuropsychopharmacology, are summarised below.
What is Opioid Use Disorder?
Opioid use disorder (OUD) is the continued use of opioids despite significant harm to a person’s health, relationships or daily life. It is a recognised medical condition, not a failure of willpower, and it can be treated. In the United States alone, OUD affects an estimated 5.7 million adults and contributes to around 55,000 overdose deaths each year. It is a serious public-health concern in many countries, including the UK.
Why does long-term pain make recovery harder?
The main treatment for OUD is opioid agonist treatment (OAT) – medicines such as methadone or buprenorphine that reduce withdrawal and cravings. This approach is highly effective, reducing the risk of death from overdose by around 50-70%.
However, up to 60% of people receiving these medicines also live with chronic pain. Persistent pain is linked to poorer sleep, greater difficulty functioning, stronger cravings, the need for higher opioid doses, and a higher chance of returning to non-medical opioid use. Long-term opioid use can also make the nervous system more sensitive to pain over time – a paradoxical effect known as opioid-induced hyperalgesia. For all these reasons, doctors and researchers are interested in non-opioid treatments that could help manage pain alongside OAT.
Why did researchers look at CBD?
CBD is a compound found in the cannabis plant. The body’s own endocannabinoid system and its opioid system overlap, which is one reason scientists have wondered whether CBD might influence pain. Earlier laboratory studies suggested CBD could have effects on the transmission of pain signals in some types of nerve pain.
Until now, though, no study had tested how CBD affects pain in people who have both OUD and chronic pain and are receiving methadone. Long-term opioid use may change how the body responds to cannabinoids, so this specific group needed to be studied directly rather than assuming results from other settings would apply.
What did the study look at?
This was a randomised, double-blind, placebo-controlled crossover study – a robust design in which each person received every treatment in turn, in a random order, and neither they nor the researchers knew which was which at the time. Twenty-three adults took part, and 22 completed all four sessions.
Each participant received a placebo and three single oral doses of CBD (400 mg, 800 mg and 1,200 mg) on separate days, at least three days apart. To separate CBD’s effects from those of methadone, the team used an “opioid-withholding” model with two phases:
- Before methadone (Pre-OAT): the daily methadone dose was delayed for about three hours, capturing the period when opioid levels are at their lowest and pain tends to be worst.
- After methadone (Post-OAT): the usual methadone dose was then given, allowing the team to see how CBD and methadone interact.
Rather than relying on people simply rating their pain, the researchers used quantitative sensory testing – standardised, controlled measurements of how the nervous system processes pain. The two main measures were:
- Descending pain inhibition (conditioned pain modulation) – the body’s natural “pain dampens pain” system.
- Pain facilitation (temporal summation of pain) – how much pain builds up with repeated stimulation, reflecting nervous-system sensitisation.
The study also looked at heat pain thresholds and tolerance, opioid craving triggered by cues, cognitive performance (memory and attention), and safety. The CBD used was a pharmaceutical-grade product given under medical monitoring – not a consumer supplement.
Important context. The CBD used in this study was a high-strength, pharmaceutical-grade prescription medicine (Epidiolex), given under close medical supervision at doses far higher than those in shop-bought CBD products. In the UK, cannabis-based products for medicinal use are unlicensed prescription-only medicines. They may only be prescribed by a specialist doctor on the GMC Specialist Register, and only when licensed treatments have not helped. This summary does not promote any medicine or treatment, and nothing here is a substitute for advice from a qualified healthcare professional.
What did the study find?
Pain, before methadone
In the period before the methadone dose, higher CBD doses were associated with a modest, dose-related change in descending pain inhibition – the body’s ability to suppress pain signals. In other words, the more CBD, the stronger this effect on dampening pain appeared to be. CBD did not meaningfully change pain facilitation, and it did not improve pain tolerance.
Pain, after methadone
After methadone was given, the picture reversed. The highest CBD dose (1,200 mg) was associated with an increase in pain sensitivity compared with placebo. CBD did not enhance methadone’s pain-relieving effects. This is an important, cautionary finding: at a high dose taken close to a methadone dose, CBD may have worked against pain control.
Opioid craving
CBD did not significantly reduce cue-induced opioid craving at any dose. There were small numerical reductions after methadone (largest at the 800 mg dose), but these did not reach statistical significance and would need to be tested in future studies.
Memory, attention and safety
Reassuringly, CBD did not impair verbal memory or attention at any dose. CBD was well tolerated overall, and all reported side effects were mild and resolved on their own.
What do these findings mean?
This was a small, early-stage study, and its main achievement was showing that this careful testing method works in a group that is difficult to study. The results suggest that CBD’s effect on pain may depend heavily on dose and on timing relative to opioid medication – helpful in one phase, unhelpful at a high dose in another.
It is important not to over-interpret these results. The study does not show that CBD is an effective treatment for opioid use disorder, chronic pain or craving, and the mixed findings, including a possible worsening of pain at the highest dose after methadone, mean firm conclusions cannot be drawn. As the authors note, much more research is needed to understand if, when and at what dose CBD might have a role.
Finding out more
Decisions about pain management and opioid use disorder should always be made with a qualified healthcare professional who knows your full medical history. If you would like to understand more about medical cannabis and whether a specialist consultation may be appropriate for you, you can complete our online eligibility check.
