Addictive disorders are a burden on both the productivity and the well-being of humanity.1 The Centers for Disease Control and Prevention (CDC) reports that every year in the U.S. roughly 600,000 Americans die from drug overdoses and health complications directly due to drug use (excluding indirect death, like homicide).2-4 Over 80% of deaths are due to tobacco, making it the leading cause of preventable death. Tobacco also has medical costs and lost productivity, adding up to more than $300 billion a year, out of an overall drug abuse cost estimated at $740 billion annually.5 Ten times as many people want to stop smoking than those who successfully can. That’s a 10% success rate, 90% relapse.

In 2013, the American Psychiatric Association (APA) published its 5th edition of its Diagnostic and Statistical Manual of Mental Disorders (DSM) with more stringent criteria for defining substance use disorders.6-8 These changes prompted an update to the estimates of substance use disorders in the United States.

Researchers estimate in the past year that the prevalence rates for successfully meeting substance use disorder criteria are roughly 20% for nicotine, 14% for alcohol, and 4% for all other drugs. They also estimated lifetime prevalence rates at roughly 28% for nicotine, 29% for alcohol, and 10% for other drugs. To put this in perspective, it means researchers estimate that more than 1/4 of all Americans have met the definition of having alcohol or nicotine use disorder at some point in their life after the APA made the criteria more difficult to meet.



Follow up studies on abstinence from overall drug dependence typically show 12-month relapse rates at roughly 40-60%, although some researchers estimate as high as 85-95%.9,10 Forty to sixty percent is comparable to the relapse rate for interventions in several chronic medical illnesses like asthma, diabetes, and hypertension. Drug dependence is a chronic medical condition that requires continued medical treatment/adherence, just like other physiological disorders. Psychedelics show promising anti-addictive effects for substances even as addictive as nicotine.

Substance Abuse Disorders and Addiction

The DSM11 defines the essential features of substance use disorders as,

A cluster of cognitive, behavioral, and physiological symptoms indicating that the individual continues using the substance despite significant substance-related problems.

The DSM also says that substance and behavioral addictions are both implicated in

…direct activation of the brain reward system, which is involved in the reinforcement of behaviors and the production of memories.

Addiction is a learned behavior characterized by changes in brain circuitry that remains after there is no more drug present in a system.12-14 The ability to learn happens through synaptic plasticity, which is the ability for neuron communication to strengthen or weaken. Addiction appears to be primarily controlled by the neurotransmitters dopamine and glutamate. There is substantial evidence that dopamine has more complex roles than its general association with reward and pleasure.

Experimental animal studies indicate both unpleasant stimuli and novel stimuli with no obvious pleasurable properties result in the release of dopamine.12 The release of dopamine serves more as an indicator for the motivational significance of rewards—behavioral cues—rather than the consumption of rewards.12,13 This is an important distinction because the mechanisms underlying drug taking are different from drug-seeking. The enhanced significance of cues associated with drug-taking maintains behavioral patterns. Substances that block the action of receptors, known as pharmacological antagonists, block the action of drug-taking. They do not instantly modify learned behavioral cues.

Persisting in specific behavioral patterns greatly complicates describing the neurobiology of addiction. This is due to the complexity in describing the physical basis of neural synapses and circuits.15 Gene and protein expression, which forms this physical basis, involves multiple signal messaging steps. On top of this, substance use, in general, causes long-lasting changes in both genes and proteins. The surrounding environment also changes these structures and plays an essential role in observably successful addiction treatment outcomes.16

Psychedelics Aid in Modifying Long-Term Behavior

The acute effects of psychedelics may synergize with the long term behavioral change protocols mediated by psychotherapy.17,18 This may be through psychedelics’ possible suggestibility, novelty, and spirituality enhancements.18-20, Some researchers, such as Dr. Stansilav Grof and Timothy Leary et al., hypothesized that the observable benefits of psychedelics depend on accompanying therapy.21

Controlled trials showcasing psychedelics’ anti-addictive properties in humans always appear to use some type of therapy.22-25 Designing controlled studies for hallucinogens is a balancing act. There are serious ethical issues with administering hallucinogens while lacking in preparation and support. However, too much preparation and support may be countertherapeutic for controls by inciting disappointment for those who did not have an impressive experience.21

It’s not completely clear that therapy is necessary with psychedelics.26 In mice, there are significant reductions in alcohol consumption habits following a single high dose of LSD.27 Multiple observational studies (i.e., surveys) suggest psychedelic use without a laboratory setting may also lead to a reduction in problematic substance use.28-30 In one study, only 10% of participants reported an explicit intention to change their disordered drinking behavior beforehand.28 So, the authors suggested the predictor for change in problematic consumption was the degree to which the experience is meaningful. Meaningful experience changes life values. They suggested meaningfulness is mediated by both the intensity of mystical experience and the degree of psychological insight.

A 2012 meta-analysis consisting of six double-blind studies (five fully double-blind) from the early ’60s and ’70s found a single LSD dose had a significantly beneficial effect in reducing alcohol misuse for six-months.22 Additional meta-analyses suggest this effect may be more related to the quality of life and general health increases.23 The experimental methodology and resulting data from this period may be somewhat questionable, but they justified further investigation nonetheless.

Subsequently, a 2015 study demonstrated the feasibility of using psilocybin to treat alcohol dependence.24 The results indicated that the participants experienced improvements largely sustained for nine months following treatment.

Preliminary findings in studies using psilocybin to treat tobacco addiction suggest they are significantly more effective than other techniques.25 A randomized controlled trial using only Cognitive Behavioral Therapy (CBT) had a 17% abstinence rate at the 6-month follow-up. Studies using nicotinic modulators bupropion and varenicline for 12 weeks daily followed up at the 6-month mark post-treatment had abstinence rates of approximately 25% and 34%, respectively.

A 2014 pilot study using psychedelics to treat tobacco addiction consisted of a 15-week CBT program where psilocybin was only used either two or three times. It is advisable to take the following results with a grain of salt because it has a small sample size (n=15). There was an 80% abstinence rate, biologically validated, after six months. Twelve participants returned after roughly 2.5 years, and nine (60%) were biologically validated to still abstain from smoking.31

These results spurred other research groups to begin more extensive clinical trials of psilocybin‘s anti-addictive effects, such as on alcohol abuse (NCT02061293) and cocaine abuse (NCT02037126).32

Ibogaine is a serotonergic hallucinogen found in plants, often used in alternative medicine as an anti-addiction drug.33 In the United States, it’s not approved as medically appropriate for any condition. Ibogaine’s complex pharmacology allows for serious adverse effects. Particularly, in scientific literature, there are many reports of its cardiotoxicity, even with a single dose. In humans, even low doses can slow heartbeats irregularly for several days after ibogaine wears off due to its bodily processing byproducts. Some researchers suggest there is enough evidence for a causal link: ibogaine may cause life-threatening cardiotoxic effects.

In light of this, a 2016 meta-analysis indicated that ibogaine reduces self-administration for cocaine, alcohol, and opioids.34 However, it still lacks changing learned behavioral cues. Ibogaine‘s anti-addictive effects warrant an investigation into structurally related compounds that may lessen its cardiotoxicity.

Treating Addiction with Psychedelics

The environment of a psychedelic treatment session is generally believed to be pivotal for positive outcomes.1,18,21-23,25,26,32,35 Also, the emotional quality of the session plays a key role in reducing withdrawal symptoms. Specifically, trust in the session guide and the experiences of interconnectedness, awe, and curiosity are the features that participant report helping them quit smoking.17

The authors of various psychedelic addiction treatment studies suggest phenomena similar to mystical effects are associated with long term abstinence.26 Griffiths et al. employed scientifically supported nonsectarian spiritual practices, such as daily 10-30 minute meditations, self-reflective journaling, and mindfulness in everyday tasks.19 Differing levels of guidance in the implementation of these spiritual practices produce differing outcomes. High dose psilocybin with standard support (7.5 hours of guidance throughout the study) significantly outperforms low dose psilocybin with standard support. High dose psilocybin with high support (35 hours) experienced diminishing returns in terms of magnitude. However, the amount of time the treatment was effective greatly improved. It is important to keep in mind that a complete transcendent experience is not necessary for successful outcomes. The important factor is a substantial increase in positive personal meaning.20

A single experience resulting in long-lasting benefits is unusual in modern medicine.20 A single experience resulting in long-lasting negative effects is well documented, e.g., trauma or Post-Traumatic Stress Disorder (PTSD). Substantially meaningful positive psychedelic experiences could function as the opposite side of this coin and create long-lasting benefits towards overall functioning.

Summary

Addictive disorders are a burden on the health and productivity of humanity. Addiction is a negative compulsive behavior characterized by a complex physical transformation of receptors due to its behavioral persistence in the absence of substances. Merely blocking the action of addictive substances is not enough to instantly transform the associative cues in learned behavior. However, there is some evidence that psychedelics can acutely affect addictive behaviors, which may synergize with psychotherapy. Preliminary results suggest substantial improvement over current addiction treatments. The enhancement of personal meaning leading to changes in life values, be it from mystical experience and/or psychological insight, appears to be a crucial element for successful outcomes.