Cannabis Holds Potential As Novel Treatment for Opioid Use Disorder

The opioid overdose epidemic is possibly the worst public health crisis in U.S. history, with some reports citing around 62,500 opioid-related deaths in 2016 alone. For comparison, that is nearly 20,000 more deaths per year than at the height of the AIDS epidemic, and a greater number of deaths in a single year than casualties registered over the entire 20-year span of the Vietnam War. In 2017, the number of opioid-related deaths grew further to 72,000 deaths – that’s nearly 200 deaths per day.

While it is known that abuse of illicit opioid drugs does contribute to this epidemic, it is thought that the major contributing factor is the over-prescription of opioid-based medications, such as OxyContin, in response to the targeted marketing carried out by pharmaceutical companies. Patients commonly experience feelings of extreme relaxation or pleasure as a side-effect of taking opioid medications, and the desire to feel this “high” can serve as a gateway to more potent and dangerous opioids, such as heroin. Opioid over-prescription is also thought to be the main reason for the recent demographic shift in opioid deaths - from predominantly affecting underprivileged, young men from ethnic-minority backgrounds, to now displaying similar mortality rates across race, gender, socioeconomic, and geographical boundaries.

Current opioid use disorder therapies

It is clear that the best way to solve the opioid epidemic is to drastically reform how opioid-based medications are prescribed to vulnerable patients. But for those who have already been exposed to opioids and developed a reliance or an addiction, it is important that there are support systems in place to assist with feelings of withdrawal and to help prevent relapse in people who are trying to overcome their dependence on opioids. Unassisted, 85% of opioid users who try to combat their addictions through abstinence-only methods will end up relapsing within a year.

The U.S. Food and Drug Administration (FDA) lists three drugs - buprenorphine, methadone, and naltrexone - as being approved for use in treating opioid use disorder (OUD). Medication-assisted treatment of OUD is certainly more effective than abstinence alone, with one long-term clinical study reporting that after a year of this assisted treatment, half of the study group reported maintaining a complete abstinence from opioid use, and after 3.5 years this number had grown to 61% of the group being opioid-free.

However, despite showing strong clinical promise, there are concerns surrounding the geographic accessibility of this treatment. Physicians and clinics that are licensed to provide this type of treatment are often concentrated in larger cities, which can be a barrier to treatment for OUD sufferers who live in more rural locations.

The link between cannabis and opioids

With the rising popularity and availability of cannabis (more states are legalizing the drug for medicinal use) and with many opioid users self-reporting the beneficial effects of cannabis in treating OUD, many medical researchers are putting this claim to the test in the pursuit of finding better OUD treatments.

Cannabinoid-1 (CB1) receptors and mu opioid receptors (MORs) are present in many of the same areas of the brain, and act largely through the same group of G-proteins. This overlap of receptors results in the linkage of both the endocannabinoid and opioidergic systems in the body. Current research supports the notion that modulating one set of receptors can influence the other, and this may have some benefit in terms of stimulating cannabis receptors to lessen opioid withdrawal, but the exact neurobiological mechanisms behind this remain unknown.

Cannabis as a treatment for opioid withdrawal

Patients with OUD are most at risk of relapsing into opioid use during the initial acute withdrawal period (the first few weeks after ceasing opioid use) and so finding effective therapies to treat withdrawal symptoms are a high priority.

Cannabinoid agonism and antagonism are thought to interfere with the opioid withdrawal response through different mechanisms, but the exact nature of these has not yet been defined. However, several pre-clinical studies on mice have supported the notion that cannabis and select formulations of cannabinoids can be effective at treating withdrawal symptoms and preventing a relapse into using opioids.

Cannabis’ classification as a Schedule 1 drug restricts the level of clinical research that can be done into the drug’s potential activity as a form of opioid withdrawal treatment, however early studies into the combined synergistic effects of low-dose cannabinoids and methadone as a way of treating OUD have shown promise. Additionally, there are many personal anecdotal accounts of people affected by OUD, who claim that cannabis use has helped to ease withdrawal symptoms when tapering down the use of, or abstaining from, opioids.

Cannabis as a first line analgesic

The opioid crisis will not cease simply because a better treatment for opioid dependence and withdrawal is found; something must first be done about the high rates of opioid exposure through over-prescription by physicians.

Opioids are most commonly prescribed to patients experiencing moderate-to-severe pain. They act by binding to opioid receptors in the brain and spinal cord which block pain signals to the brain, lessening the patient’s discomfort. Opioids also cause the release of large amounts of dopamine into the body, which assists with the feelings of pain relief, but these pleasant effects of the dopamine rush are also responsible for the addictive opioid “high”.

Recent studies have highlighted the potential for cannabis, or cannabis-based medicines, to exhibit similar analgesic behavior for many of the same conditions that are currently treated with opioids. A comprehensive review of research into cannabis as a pain-reliever revealed that cannabis shows promise in the relief of neuropathic, inflammatory, cancer-related, and chronic pain.

While cannabis treatment alone is not effective to the same degree as opioid treatment in terms of the amount of pain relief experienced by the patient, research into the use of low-dose THC (Δ9-tetrahydrocannabinol, a major component of cannabis) in conjunction with lower-potency morphine for pain relief in mice, indicates the two may have a synergistic effect. The outcome is a treatment that provides similar pain-relieving effects to opioid treatment alone, but with fewer detrimental side-effects observed, though once again, the scheduling of cannabis as a Schedule 1 drug has made it hard to clinically research whether this effect is also seen in humans.

Shortcomings of cannabis therapy

It should be noted that cannabis therapy would not be without its own shortcomings. The large number of strains of cannabis available and their differing cannabinoid profiles and health effects introduce a wide margin for variation in the ability of cannabis to treat OUD symptoms or be an effective pain-reliever.

There is also a lack of data concerning the long-term effects of cannabis use and the development and severity of cannabis use disorder (CUD); though CUD is more commonly associated with the use of high-THC cannabis, which is not typically used medicinally.

The largest barrier to the further research that is needed in all areas of cannabis medicine is the continued status of cannabis as a Schedule 1 drug. This scheduling does not recognize cannabis as having any medical benefit and makes it significantly harder for research to be carried out on the drug. Should the U.S. begin proceedings to reschedule cannabis, similar to what is currently happening in the United Kingdom, the move could open the door to new avenues of research; this could, in turn, have major benefits for those with OUD, as well as many other medical conditions.