From Crisis To Cure: Psychedelics & Opioid Use Disorder

In 2021, over 80,000 Americans died due to an overdose that involved opioids – representing 75% of overdose deaths in the country. That’s 1,500 deaths per week due to an overdose involving one or more opioids.

While treatments are available for opioid use disorder (OUD), they’re not perfect. They require strict adherence to taking medications every day, there’s social stigma behind the medications used and the legal requirements patients must go through to attain them, and some medications used to treat OUD are opioids which can cause fatal overdose themselves.

This week, we’re breaking down a review article that highlights research to date and future potential of several psychedelics for treating OUD. But first, we need to go over what a review article is, and how it differs from an original research article.

 

Research Articles vs. Review Articles

Research articles summarize what happened in a specific clinical trial. They report original research findings. Research articles contain sections such as methods, which describes the method of study used, and a results section, detailing the results of the research. Research articles are primary sources – the people who conduct the research also write the article summarizing what they did and what they found.

A review article attempts to summarize the current state of scientific understanding of a topic. These articles analyze existing published research to give a “snapshot” of the current state of research. Review articles are considered secondary sources. The author is giving a “secondhand” account of someone else’s work.

As I see it, review articles are important because:

• Our understanding of medical science changes over time. Otherwise, we’d still be bloodletting and throwing leeches onto every limb of your body (medical leeches ARE still a thing, by the way). Review articles help summarize different studies across time to give us an idea of where we currently stand in our knowledge and applications.

• Review articles help summarize the problems still present – particularly large, systemic problems. A primary research article can do a wonderful job of explaining, based on the results of a study, why treatment X appears to work better than treatment Y for Z disease under certain conditions. But evaluating systemic, big picture problems is usually beyond the scope of a research article.

So – we have different types of articles to answer different types of questions.

If your question is, “Compared to drug X, is psilocybin effective for treating post-traumatic stress-disorder (PTSD) in United States veterans between the ages of 30 and 40 years?”, then a research article is likely the best choice. You’ll need to provide the clinical trial and results yourself, though. Better break out the bootstraps.

If your question is, “Do psychedelics show potential for treating opioid use disorder?”, then a review article is likely better – because the scope of this question is broad, answering it requires evidence from more than one trial. We need a summary of available evidence, and we can consolidate info from lots of other studies into one nice, neat document.

Now that we’ve reviewed what a review article is, we’ll enter discussion of today’s article – “Hallucinogenic potential: a review of psychoplastogens for the treatment of opioid use disorder”.

 

Theory- How Psychedelics Are Proposed to Work for OUD

As defined by the Centers for Disease Control and Prevention (CDC), opioid use disorder (OUD) is “a problematic pattern of opioid use that causes significant impairment or distress”. Opioids are medications which interact with nerve cells in the brain and body to reduce both feelings of pain and the intensity of pain signals. Opioids carry a high risk for misuse, abuse, and addiction.

Quick OUD facts:

• Anyone can be affected by OUD – regardless of your income, social class, race, gender, sexual orientation, profession, hair color, eye color, foot size, whatever.

• Approximately 5.6 million people in the U.S. experience OUD – and this may be underreported.

• Stereotypes portray people with OUD as “junkies”, “addicts”, and other derogatory terms which attempt to tie the condition to the person’s (purported lack of) character and a failure of the individual. Reality, on the other hand, shows it’s possible to develop OUD from using prescription opioids as prescribed and directed by your doctor. Those pesky facts show us that the majority of Americans who use heroinstarted doing so after being prescribed an opioid.

It’s proposed that psychedelics may be an effective treatment for OUDdue to their ability to rapidly induce neuroplasticity.

We must nail down our understanding of neuroplasticity before proceeding.

Neurons are the fundamental cells of your nervous system – including your brain. When neurons connect and work together, it’s called a neural network. Neuroplasticity is the ability of neurons and neural networks to grow and reorganize themselves.

If neuroplasticity sounds scary – “I don’t want to change how my brain functions! What if it changes who I am?!” – that’s a totally normal response. Try looking at it this way: have you ever learned new information? Or learned a new skill? Then you have engaged in neuroplasticity and “changed” who you are. In order for you to learn how to throw a football or ride a bike or walk down the hallway without spilling your coffee, neurons in your brain had to make friends with a LOT of other neurons. Neurons weave webs across your mind to ensure that you not only learn to ride that bike, but you also don’t forget how after you step off (imagine how discouraging it’d be if you had to re-learn the process each and every time you wanted to ride). Neuroplasticity is something our brain does naturally – and our capacity for plasticity has evolved over thousands and thousands of years.

Current treatments for opioid use disorder (OUD) include buprenorphine, buprenorphine/naloxone, and methadone. These treatments do not induce neuroplasticity to any degree. This means they have zero ability to impact a patient’s attitude. They work to address the physiologic manifestations of addiction – for example, reducing cravings and preventing opioid withdrawal. They require strict, long-term adherence to treatment – a commonly referenced reason for treatment failure. Safety is a concern as well – approximately 4% of monthly overdose deaths in the United States involve methadone.

On the other hand, psychedelics such as ibogaine, psilocybin, and DMT are known to quickly trigger changes to connections inside our brain – specifically within the prefrontal cortex (PFC). I’ll now shamelessly plug a previous article, “This is Your Brain on DMT”, which discusses brain function and effects of DMT on triggering said connections.

Research has shown that people experiencing addiction have atrophied, dysfunctional neurons within their PFC. It makes sense, then, that treatments which can rapidly establish new neuronal connections could not only treat addiction in a timely fashion, but also in a long-lasting manner that doesn’t require daily or twice-daily medication.

 

Reality- How it’s Looked in Practice to Date for Treating OUD

Ibogaine

Ibogaine is a complex substance with numerous effects in the body. Specifically, ibogaine:

• Acts as an agonist at 5-HT2A, 5-HT3, and muscarinic receptors

• Antagonizes nicotinic acetylcholine receptors

• Antagonizes NMDA glutamate receptors

• Acts as an agonist at mu and kappa opioid receptors

This review identifies 8 studies – clinical trials, case reports, case series, retrospective studies, and observational studies – which evaluate ibogaine for treating OUD. Results vary:

• One case series evaluated two patients and noted that the patients sustained abstinence from opioids for 2 to 3 years following a week of treatment with ibogaine. But in other, larger studies, abstinence rates were smaller and shorter lasting. One retrospective study with 73 participants found that, when followed for more than one year after ibogaine treatment, 36% of participants were abstinent from opioids, and 45% reported decreased opioid use.

• Several studies report effectiveness at treating opioid withdrawal symptoms, as well as reducing cravings for opioids.

“Classic” Psychedelics- LSD, Psilocybin,  and Ayahuasca

The 5-HT2A agonists are referred to as “classical psychedelics”. We’ve discussed the science and pharmacology of these drugs previously, so I won’t go in-depth here.

Instead, let’s hit some study highlights:

• A study by Pisano, et al. found that, among people who reported having an opioid use disorder, those who used psychedelics had a 27% reduced risk for opioid dependence. (Fun fact: in this same study, the researchers noted that cannabis use decreased the risk for past year opioid abuse by 55%. Another glaring example of the war on drugs leading to devastating consequences and the deaths of millions of people. “SaVe ThE cHiLdReN”, indeed.)

• A study by Argento, et al. from 2018 found that recent psychedelic use had a protective effect on both opioid use and suicide risk among marginalized women (defined, in this study, as “marginalized and street-involved women sex workers” in Vancouver

• Another study by Argento, et al. from 2022 found psychedelic use to be associated with a reduction in daily opioid use among self-reported illicit drug users.

Ketamine

Ketamine is a derivative of phencyclidine (PCP), developed with the intent of having fewer psychodysleptic (out of body experience, hallucinations, delusions, etc.) effects than its parent compound. Ketamine is effective for treating refractory major depressive disorder, and has shown potential for treating substance use disorders including OUD.

One study evaluated high- and low-dose ketamine in conjunction with psychotherapy for treating 70 patients with heroin addiction. Researchers found that the high-dose group experienced an immediate reduction in cravings following ketamine infusion. Another study conducted by the same research group found that 50% of patients who received multiple ketamine doses remained abstinent from heroin after one year, compared to 22% of patients who received only a single ketamine dose.

 

Conclusion

While the data above is exciting, there’s still plenty of work to do before we know the true effectiveness (or lack thereof) for psychedelics in treating OUD.

A major issue with many of the studies linked above is the lack of randomized, prospective, placebo controlled, blinded clinical trials. Instead, most studies above are retrospective – looking back at data and attempting to find patterns. This is an excellent method for identifying possible topics for future clinical research, but it’s not a great way to definitively know if a treatment is effective. An issue with using “looking back” sort of studies is that there could be other factors unaccounted for which could play a minor or major role in the patient’s reduced opioid use.

The good news? These studies are going to happen. The preliminary evidence is too strong. The dam is breaking. That doesn’t mean results will be positive. But it does mean we’ll finally begin catching up on over 50 years of lost research, and we’ll finally start answering questions about the medical capabilities of psychedelics – including their use in ending the opioid epidemic.

 

References: Referenced study