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How a Psychoactive Root Fights the Root Causes of Addiction
Can We Use Illicit Drugs to Treat Addiction?
Anecdotal and preclinical evidence have implicated a number of hallucinogenic drugs as being effective treatment tools for addiction. Treating a drug habit with more drugs may sound counterintuitive... until you come to understand what addiction is and the nuances of classifying illicit substances
I first came across Matthew Morello’s story when I watched this episode of HBO’s “Vice” back in 2014. Vice News is known for covering provocative, and often controversial stories using up close and daring investigative practices. Vice has produced a plethora of sensationalized journalistic pieces throughout its existence, many are of dubious integrity yet interesting enough to inspire further critical research. The following story of Matt is one such story that has stuck with me over the years, the story of a man who cured his heroin addiction with a powerful hallucinogen called Ibogaine.
A Miraculous Story
All throughout my undergraduate career as a neuroscience major, I've been intently exploring questions surrounding psychopharmacology and drug addiction. So when I revisited the memory of Matt's story, I could not resist the impulse to re-examine the topic with the knowledge and research skills I have since acquired. This documentary was claiming that this psychedelic drug 'ibogaine' could cure heroin addicts when nothing else could. How is that possible? What is ibogaine and how has it been used to treat addiction? How successful is it in curing addiction? If it is successful, then what are the underlying biological mechanisms for this? Does this mean it’s possible to effectively cure addiction using other mind altering drugs?
Let's start by looking at the details of the case documented by Vice. Matt was addicted to heroin which is one of the deadliest addictions a person can have. Heroin kills around 5 Americans per every 100,000 of the population according to the CDC. In 2011, after years of struggling with his addiction and unsuccessfully trying different forms of detox and rehabilitation, Matt was given an opportunity to try an unconventional form of treatment that was rumored to be the closest thing to a magical cure as it gets. A spiritual ceremony centered around a psychedelic root.
Traditionally, young men of the West African religion Bwiti perform this ceremony as a rite of passage. During the ceremony, the young men take ibogaine with the intention of receiving spiritual insight that is vital to their custom and beliefs. Matt’s intention, however, was to be rid of his addiction to get another shot at life. And as the episode shows, it works. By the time the episode airs after being shot, we are told that Matt had been clean for 14 months.
I did some research and discovered that Matt is still clean, nine years after the ceremony took place. Nearly a decade of sobriety is an achievement almost unimaginable for many heroin addicts, so clearly something worked in this case. Matt has since dedicated his life to utilizing the powers of plant medicine and ayahuasca to help others struggling with mental illness and addiction in the same way he was helped.
But Matt’s story is only the beginning of my research into magical cures and the neurochemistry of addiction. Before we go any further, I think it’s important to cover some of the basic understandings we have about the psychology and neurobiology of addiction.
Read More About Matt's Work
Understanding Addiction
Drug addiction ( or substance use disorder) is referred to in the DSM 5 as a disease that affects a person's brain and behavior and leads to an inability to control the use of a legal or illegal drug or medication. Historically, drug addiction was widely considered to be indicative of some moral or disciplinary deficit. And more often than not, people blamed the drug addict for their own suffering. Discoveries in neuroscience and psychology have since begun to tell a different story, and the overwhelming majority of researchers today agree that addiction is a disease rooted in biology. According to this model, for largely unknown reasons, some people are naturally extra sensitive to the mechanisms by which recreational drugs influence behavior. How is this so?
Rewarding drugs are known to activate what is called the mesolimbic dopamine pathway, this is what lures people to illicit drugs in the first place. They feel good. Organisms evolved the mesolimbic system because it kept them alive by making vital things (like food and sex) chemically and psychologically rewarding. For most people, the mesolimbic system does a great job at keeping them alive and healthy. But, as stated earlier, the brains of some people are highly susceptible to the mesolimbic dopaminergic rewarding effects of addictive drugs; so much so to the point that drugs become neurochemical hijackers of the neural processes that motivate behavior. This is how people become addicted to drugs. The incentive of guaranteed reward via activation of the mesolimbic system comes to dominate processes that would normally override drug seeking behaviors.
The first step most drug addicts take to get sober is detox. Most of the time this requires inpatient care since the urge to use is essentially physiologically impossible for the addict to overcome by their own free will. After the drug leaves the addicts system, professionals help the addict learn coping techniques that slowly help to chip away the hold that the addictive pathways have over the brain. Oftentimes this involves replacing the habit of drug use with a new healthier habit or passion that the brain can focus on. Some professionals might prescribe patients a drugs that negates the effects of their drug of abuse (such as Wellbutrin for nicotine addiction). These cognitive behavioral and pharmacological methods of treatment work slowly and are in no way guarantee sobriety. This is why claims made by proponents of ibogaine and other rapid psychoactive drug addiction treatments are so remarkable and fascinating. How might a psychoactive drug work to interrupt a process and impulse that has been so deeply ingrained by the mesolimbic dopamine system by repeated drug use? Is Matt’s experience with ibogaine proof of a miraculous neurochemical action of some psychoactive drugs that cures addiction?
Evidence for Ibogaine Treating Addiction
If we are to understand how ibogaine changes the brain and cures addiction, we should first investigate the legitimacy of the assumption that it does work. So let’s talk about ibogaine.The compound Ibogaine comes from the bark of the roots of a tree known as Tabernanthe Iboga. Its psychoactive properties were originally discovered and used by tribes living in central Africa where it developed an important spiritual and medicinal significance.
The first report of ibogaine being an anti-addictive agent comes from an American scientist by the name of Howard Lotsof. Reportedly, Lotsof was a heroin addict who happened to stumble upon ibogaine which he used to kick his own drug habit. After this, Lotsof spent the rest of his life researching and publishing papers on the benefits of ibogaine until his death in 2010. His work turned out to be quite influential, interest in the phenomenon of ibogaine as an anti-addictive drug exploded across Europe in the latter portion of the 20th century. But by the year 2000, ibogaine had become illegal in The United States and in many parts of Europe, severely restricting prospects to systematically research its anti-addictive benefits.
The legal status of ibogaine makes it difficult to find any evidence for it being an effective treatment for addiction. The bulk of evidence for ibogaine effectively treating addiction is anecdotal in nature. Although scientists tend not to regard anecdotal reports as particularly compelling evidence, stories and individual experiences have an emotional resonance to them that captivate people’s interest. And public and personal interest helps to motivate legislation as well as scientific investigation.
Firsthand reports of ibogaine successfully treating addiction come from scientific and nonscientific sources alike. Many cases of ibogaine treatment take place because someone (a drug addict) became aware of its existence and sought out this underground and illegal treatment as a last resort. Ibogaine treatment is often overseen by non-professional or semi-professional clinicians and is administered in countries with fewer restrictions on the drug. The typical ibogaine treatment session usually looks something like the following:
The patient/addict reports to the clinic early in the morning where they are orally administered one dose of ibogaine HCL
Withdrawal from their drug of abuse sets in around the time the ibogaine begins to take effect
The patient lays awake in a dark calming environment for the duration of the treatment which can last anywhere from 12-24 hours
According to subjective accounts of ibogaine treatment patients, the experience is emotionally intense and often unpleasant in many ways. The drug causes hallucinations similar to those experienced by people under the influence of drugs such as LSD and magic mushrooms. Many patients have reported experiencing dreamlike visions involving emotionally significant memories. After about 8 hours or so, the intensity of the sensory hallucinations diminishes and the outward experience becomes more inward oriented and introspective.
Many, but not all, anecdotal reports describe a fair degree of mental or spiritual insight and newfound meaning. One account from an Erowid.com user describes the following:
“I opened my eyes and asked, simply, what I could do to best improve myself. It was a very basic, general question, but considering how strongly this iboga was affecting me, it was the best I could muster. I felt compelled to generate at least some kind of question. After I asked the question, I was shown my guide. His face was porcelain smooth, and matching white robes hung from the base of his head down to his feet. I mostly only saw his face, very close to mine. He spoke directly to my mind in a very subtle way, it felt like remembering a conversation, but it happened in real time.”
One common method of testing the addictiveness of a drug involves giving access to the drug to lab animals and seeing how often they self administer the drug under various conditions. Humans and animals tend to get addicted to the same drugs which makes animal self administration a good proxy for human addiction. Some of the most compelling data supporting ibogaine’s effectiveness comes from experiments that used ibogaine on animals addicted to drugs like morphine and cocaine. It’s been shown that those animals who were given ibogaine were less likely to self administer their drug of abuse than those who had not.
Case studies by individual practitioners or organizations who use ibogaine to treat drug addiction are perhaps the most important evidence we have for ibogaine. Some reports say that a single ibogaine treatment is effective for helping former opiate addicts stay clean for up to six months following an ibogaine treatment. Unfortunately, even with these findings, no proper controlled study has been conducted to investigate the effects of ibogaine on drug cravings.
So how do we answer the important question? Is ibogaine effective for treating drug addiction? There are a number of ways to answer this question, but unfortunately none of these ways involve meta-analysis of double blind placebo controlled clinical experiments. If you look only at anecdotal reports, as I did when I first saw the Vice documentary, you may be inclined to say “yes, ibogaine is a magic bullet cure for addiction”, certainly many people who opted to try ibogaine for their addiction believed this. One has to wonder whether or not the expectation of ibogaine curing their addiction had anything to do with the success they experienced; something that could be determined by a double blind randomized placebo experiment.
I’ll avoid trying to answer the question of why there have not been controlled experiments on ibogaine. The reason is likely a complex jumble of sociological and legal explanations that require their own article to fully understand. For now, I’ll focus on trying to understand how ibogaine might treat addiction.
What are the Pharmacological Anti-addictive Properties of Ibogaine ?
In pharmacology, ibogaine is what’s known as a “dirty drug” because it interacts with many different neurotransmitter systems and many different receptors. This makes it harder to understand what it does and also how it might be distributing drug addiction. Pharmacological effects of ibogaine include but are not limited to:
-Antagonism at the NMDA glutamate receptor
-Binding to kappa and mu opioid receptors
-Binding to sigma 2 receptors
-Binding to sodium ion channels
-Binding to the serotonin reuptake transporter
-Antagonism at the nicotinic acetylcholine receptor
-Agonism of the 5HT2a and 5HT3 serotonin receptors
-Agonism at the muscarinic acetylcholine receptor
Multiple models of ibogaines mechanism of anti-addictive effects have been proposed based off of it’s numerous pharmacological actions
Theories of Ibogaine Anti-addiction
Action on Opioid Receptors
Ibogaine is metabolized into the active metabolite noribogaine which has a stronger effect on the mu and kappa opioid receptors. It has been hypothesized that the lipophilic ibogaine molecule is stored in fatty tissue in the brain and then slowly releases over an extended period of time to interact with opioid receptors thus limiting withdrawal effects felt in the absence of heroin or whatever opioid was being abused.
Others believe that ibogaine modulates complex chemical messages that typically occur when opiate drugs bring to opioid receptors and changes the way they interact with opiate drug molecules.
Ketamine
The dissociative anesthetic drug ketamine has become a hot topic in clinical psychology for its rapid acting and enduring antidepressant effects. The drug has been used to treat many patients with treatment resistant depression, and has had much success. Some experts have implicated ketamine as a resource to combat addiction. And indeed there are studies showing a reduced risk of relapse for patients with alcohol and cocaine addiction. Ketamine is similar to ibogaine in that there is a striking lack of controlled clinical trials in its anti addictive benefits and most evidence for its effectiveness come from first hand accounts of a collection of case studies. Another thing ketamine and ibogaine have in common is that their neural mechanisms of anti-addiction are shrouded in mystery with a handful of theories explaining this phenomenon.
Plasticity and BDNF
Ketamine blocks NMDA glutamate receptors which may inhibit glutamatergic changes that mediate anxiety and depression which contribute to addiction. These changes increase BDNF levels (which has been shown to be low in addicted patients) which may build and strengthen neural connections that do not reinforce drug associated pathways
Subtitle
(Traditional psychedelics effects on the brain and how that may interact with the addicted brain)
So Can We?
Psychoactive drugs are powerful. Some make us feel good and can give us life changing experiences, others (and often the same ones) can traumatize us or ruin our lives. All of these effects depend on a chain of chemical events that occur under unimaginably complicated biological conditions. A commonly repeated phrase tells us that no two people respond the same way to the same drug. And to take that even further, no two drug experiences (even with the same drug in the same person) play out in the same way. This I think is what makes psychoactive drugs such a fascinating topic, nothing is more interesting than a novel state of mind. Some people become so enthralled with the novelty provided by drugs that they become unable to endure existence in the absence of them. This of course is not because they are flawed, but because their brain is hardwired to seek out altered consciousness once given a taste of it. At a certain point, it becomes unclear to what extent a drug user's brain and mind is a consequence of their innate biology, and to what extent they are a consequence of a chemical produced in a lab or grown in a jungle in South America.
Because addiction depends on so many different biological, experiential, and chemical factors, it seems like the most likely that the best way to combat it also depends on multiple factors. So perhaps some ibogaine or ketamine patients improved because of the way their drug of abuse was interacting with their brain, and perhaps others improved because of the therapeutic effects the drug experience had on them. Or most likely it was some combination of both effects or other effects of these psychedelic drugs. Since these seemingly magical drug cures do so much to the brain, it makes sense that some of the contributing factors to someone’s addiction will be influenced one way or another.
What can we take away from this? Well, it seems obvious that some psychoactive drugs can treat addiction… However, that does not mean that such drugs will cure addiction. Until more clinical research is done on ibogaine or ketamine or other hallucinogens, all we can say is maybe. At this juncture, addicted seeking psychedelic treatment should also be supplementing CBT tactics in addition to their trip. Because it seems like most addicts who recover and stay clean did so by finding some form of sustainable happiness and new meaning. An increase in personalized medicine in the future might see the development of specific treatment programs that target the likely causes of someone’s addiction. I hope to see a future where a psychedelic treatment session is a standard procedure, and not something worthy of being followed by a camera crew from a controversial media outlet.