Motivation and emotion/Book/2020/Psychedelic treatment of addiction

Psychedelic treatment of addiction:
How can psychedelics help in treating addiction?

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Overview

Addiction is a chronic condition that has the ability to cause death and tear lives apart. There are many theories about what causes addiction, with research identifying biological, psychological, and social influences that may lead to the manifestation and maintenance of addiction. Unfortunately, the treatment of addiction is not an exact science. Although it seems counterintuitive to treat drug addiction with drugs, psychedelics show great promise for the treatment of addiction. Research on using psychedelics to treat addiction was a popular field in the 1960s and, after a hiatus, research has resumed.

Research has shown that classic psychedelics act on the serotonin system of the brain, allowing for profound permanent changes to be made. Studies consistently show that psychedelics help treat addiction. This effect has been hypothesised to occur due to the effects of psychedelics on brain physiology and through various psychological effects that allow for patients to feel more motivated to get better through increased self-efficacy, improved mood, and personality changes. Despite these promising results, research on psychedelics and addiction is still in its infancy, with a long way to go before it can be prescribed safely.

Case study: Gordon McGlothin Gordon McGlothin had been smoking more than 20 cigarettes a day since he was 15 years old. Gordon had tried nicotine replacement therapy, psychotherapy, and going "cold-turkey" with no luck and constant relapses. After years of trying and failing, when he was 65 years old, Gordon's friend referred him to a clinical trial for a new treatment for tobacco addiction. Researchers in the trial asked Gordon to take a small blue pill that would change his life. Gordon later found out this pill was psilocybin, but little did he know at the time, that taking that one pill would mean that he would never smoke a cigarette again (Lawrence, 2014).

Psychedelics

Psychedelics, (also known as hallucinogens, entheogens, psychointegrators, psychotomimetics, and serotonergic hallucinogens) are powerful psychoactive substances that are most commonly used for recreational purposes (Nichols, 2016; Winkelman, 2014). The term psychedelic was coined by Humphrey Osmond in 1957, to mean "mind-manifesting" which he derived from the Greek words (psyche “soul, mind” and delein “to manifest”). When ingested, psychedelics have been known to alter cognition (thinking, perception), mood, and affect as well as cause auditory and visual hallucinations (Nichols et al., 2017).

Currently, psychedelics are classed as a schedule I substance in most parts of the world, alleging that they have high abuse potential and no medical use, despite offering no dependency and a high degree of physiological safety (Nichols, 2004; Winkelman, 2014). Psychedelics were researched with promising results in the 1950s and 1960s for medical treatments (Winkelman, 2014). In the 1970s, research into psychedelics was banned due to the fallout from the war on drugs, which made it difficult for researchers to legally obtain psychedelics and receive funding (Garcia-Romeu et al., 2014; Winkelman, 2014). However, medical research using psychedelics has gradually increased in the last few decades (Bogenschutz & Pommy, 2012; Garcia-Romeu et al., 2014).

Types of psychedelics

Figure 1. Psilocybin occurs naturally in some mushrooms

There is specific clinical interest in psychedelics that directly affect the serotonin system, often referred to as "classic psychedelics", serotonergic psychedelics or serotonin 5-HT_2A receptor agonists or partial agonists (Nichols et al., 2017). Examples of serotonergic psychedelics include:

• Lysergic Acid Diethylamide (LSD)
• Psilocybin
• Mescaline e.g. Peyote
• N,N-Dimethyltryptamine (DMT) e.g. Ayahuasca

The effects of psychedelics

Figure 2. Psychedelics can cause visual hallucinations

According to Nichols (2016), psychedelics cause users to experience a variety of phenomena including:

• Altered somatosensory, visual, and proprioceptive sensations
• Changes in perception including feeling as though time has slowed down or sped up
• Effects on cognition
• Effects on mood including feelings openness, trust, and happiness
• Effects on memory
• Spiritual or mystical experiences
• Visual and auditory hallucinations
• Audio-visual synaesthesia
• Positive experiences of depersonalisation or derealisation

Figure 3. Psychedelics can cause pupil dilation

In addition, Schmid et al. (2015) identified physiological effects of psychedelics which include increased:

• Blood pressure
• Heart rate
• Body temperature
• Pupil size
• Plasma cortisol
• Prolactin
• Oxytocin
• Epinephrine

Figure 4. The left pre-frontal cortex (PFC)

Although the exact mechanism of action is unclear, it is accepted that the agnostic actions at the 5-HT_2A receptors in the cortical areas of the brain play an important part in the effects of psychedelics (Vollenweider et al., 1998; Vollenweider & Kometer, 2010; Bogenschutz & Pommy, 2012; Nichols, 2016; Carhart-Harris, 2018). This conclusion has been drawn due a number of studies, including a study by Vollenweider and colleagues (1998) showing that, when administered the 5-HT_2A antagonist, ketanserin, none of the psychoactive effects of psychedelics was experienced.

Per the name, serotonergic psychedelics (classic psychedelics) bind to serotonin receptors and subtypes to produce their effects. Although psychedelics bind to a number of serotonin receptors (as well as dopamine and glutamate receptors), they show a high affinity for the 5-HT_2A receptor (Vollenweider & Kometer, 2010; Bogenschutz & Pommy, 2012). The stimulation of the 5-HT_2A receptors cause a glutamate-dependent increase in activation of the pyramidal cells in the pre-frontal cortex (PFC) indicating that classic psychedelics have the ability to alter and control the activity of the PFC (Vollenweider & Kometer, 2010; Bogenschutz & Pommy, 2012).

Addiction

West and Brown (2016) define addiction as “a syndrome at the centre of which is impaired control over a rewarding behaviour, acquired as a result of engaging in that behaviour” (p. 12). Although there are many types of addiction, currently the DSM-5 recognises substance-related and addictive disorders (gambling disorder).

Two major pathways have been identified in the manifestation and maintenance of most addictions, the dopamine reward system and endogenous opioid system (Koob & LeMoal, 1998; West & Brown, 2016). However, there are a range of biological, psychological, and social theories of the causes of addiction - all emphasising different reasons as to why addictions manifest and how they perpetuate.

What causes addiction?

Figure 5. The biopsychosocial model of health

West and Brown (2016) identifed several popular theories of addiction:

Psychological theories

• Theories of motivation (addiction is due to a malfunction of motivation)
• Cognitive theories (suggest that expectation of positive consequences or reduction of aversive experiences can drive one to engage in an addictive behaviour, which can then strengthen reward pathways in the brain)
• Behavioural theories (focus on directly observable factors that contribute to the manifestation and perpetuation of addiction)

Social and cultural theories

Social learning theory suggests that addiction is caused by learning through the environment via modelling and vicarious learning (through parents, peers, etc.) as well as one’s self-efficacy (Bandura, 1977; West & Brown, 2016).

Biological theories

Hypothesise that addiction is due to biological causes (West & Brown, 2016).

• Personality theory of addiction: suggests that one can have a vulnerability to addiction if they have a disposition to certain personality traits (Cloninger, 1987; West & Brown, 2016)
• Genetic vulnerabilities: suggests that people inherit an increased likelihood of developing substance-use dependence (Kendler et al., 1997).

How is addiction treated?

Standard addiction therapy includes (NIDA, 2019):

• Behavioural counselling and psychotherapy
• Medication to treat co-occurring disorders e.g. anti-depressants, anti-anxiety medication (anxiolytics)
• Medication to treat withdrawal, examples of medication include:
  • Methadone and buprenorphine for opioid addiction
  • Nicotine replacement therapy for tobacco addiction
  • Naltrexone, acamprosate, and disulfiram for alcohol abuse

Psychedelics are a schedule ___ drug in most parts of the world: Schedule III Schedule II Schedule I None of the above Addictions manifest because of: Biological vulnerabilities Psychological influences Social/environment influences All of the above

Can psychedelics help treat addiction?

Figure 6. Substance-use disorder is a type of addiction

Research on psychedelics and addiction began in the 1950s with the primary focus being on treating alcohol addiction using a high dose of psychedelics in hopes of facilitating a mystical experience as it was thought to cause positive personality changes.

Although many studies on psychedelics and addiction are on alcohol, a study conducted by Savage and McCabe (1973) focused on using psychedelics as a treatment for opioid addiction. Using biological measures (such as urine and blood tests), researchers found that those who were in the LSD treatment group were more likely to abstain from using heroin; the abstinence rates after a 12-month follow up were 25% for the LSD group and 5% for the control group (Savage & McCabe, 1973).

Time and time again, studies have shown that patients with addictions who are treated with psychedelics have better outcomes than their controls. An early meta-analysis conducted by Abuzzahab and colleagues (1971) found that a single dose of LSD allowed for a 50% better outcome for the treatment of alcoholism compared to control groups. In support of this, a more recent meta-analysis conducted by Krebs and Johansen (2012) showed significant effect in the treatment of alcoholism with LSD in comparison to a control. Specific to this meta-analysis, 325 participants were treated with LSD (with 211 controls), after a follow up period 59% of participants treated with LSD improved in comparison to a 38% improvement in the control group.

Due to these promising results, the first modern study on psychedelics and addiction was conducted in 2014 by Johnson and colleagues. Johnson et al. (2014) focused on using psilocybin with cognitive-behavioural therapy (CBT) for smoking cessation. Using breath carbon monoxide and urine testing, it was found that 80% of the participants stopped smoking at a six-month follow up and 67% of participants had continued to abstain from smoking at a 12-month follow up. In support of these previous studies, a more recent study conducted by Bogenschutz et al. (2015) on alcohol addiction and psilocybin showed that, after the of psychedelics, alcohol-use decreased. These studies show great potential for the treatment of addiction especially as it allows for people to have a physiologically safe option to treat their addiction.

How do psychedelics help treat addiction?

Unfortunately, the exact mechanism of action is still unclear. However, researchers have hypothesised that psychedelics can help treat addiction through complex interaction of different physiological and psychological effects.

Focus questions Why do the serotonin enhancing properties of psychedelics help with addiction? How do psychedelics re-wire the brain? What are the psychological effects of psychedelics that help addiction? What role do self-efficacy, personality, and mood play in addiction?

Physiological effects

There are a range of physiological effects as a result of psychedelic use, most of these changes are a result of the psychedelics' effect on the serotonin system.

Effects on neurotransmitters

Figure 6. Chemical structure of serotonin (5-HT)

Psychedelics act as an agonist or partial agonist to serotonin (as well as dopamine and glutamate) receptors, especially the 5-HT_2A receptor. It is hypothesised that the improved recovery outcomes for patients with addictions when treated with psychedelics is due to the psychedelics’ effect on the serotonin system (Bogenschutz & Pommy, 2012; Winkelman, 2014; Nichols et al., 2017).

Winkelman (2014) posits two ways in which the serotonergic effects of psychedelics people with addiction:

1. Psychedelics enhance serotonin which could be depleted due to chronic drug use and this allows the patient to better regulate their overall wellbeing.
2. Serotonin acts as a neuromodulator (a regulator) to other neurotransmitter systems and therefore, the enhanced serotonergic activity as a result of taking the psychedelic cascades into other neurotransmitter systems that may also be depleted or over-active due to chronic drug use.

Bogenschutz and Pommy (2012) also note the importance of psychedelics’ effects on the serotonin system as it can reduce cravings. The phenomena of "craving" involves the brain’s reward system and the brain’s serotonin system. It is believed that augmentation of the serotonin system as a result of psychedelic use reduces cravings by reducing stress, improving mood, reducing anxiety, and reducing a risk of relapse.

Neurophysiological effects

It has also been hypothesised that psychedelics are able to "re-wire" and re-set the brain back into a pre-disease state, similar to what a computer re-boot might do (Carhart-Harris et al., 2012; Nichols et al., 2017). Using blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI) Carhart-Harris and colleagues (2012) have identified several regions of the brain that show decreased activity after the consumption of psychedelics, indicating that these areas of the brain are disintegrating (breaking down connections). It is therefore believed that psychedelics allow the brain’s networks and connections that are responsible for addiction to be disrupted and broken. After the psychedelic-experience is over, the networks re-wire and re-connect in "healthy ways" to the state it was before the addict became addicted (Carhart-Harris et al., 2012; Nichols et al., 2017).

Content check-in Gordon recently took some psilocybin and as a result, he no longer smokes cigarettes. What might have happened to his serotonin system that aided in his recovery? Answer There may have been three different processes: Gordon's serotonin might have gotten back to normal levels after years of smoking Gordon's serotonin is acting as a neuromodulator his other neurotransmitters through a cascading effect The augmentation of Gordon's serotonin system as a result of consuming psilocybin has reduced his cravings by reducing his stress, improving his mood, reducing his anxiety, and reducing his risk of relapse|}Taking psilocybin might have allowed Gordon's brain to return to a ___________ state similar to what a computer re-boot might do. Answer A pre-disease state|} Psychological effects There are are a rang of psychological effects that occur due to psychedelic use. Researchers have identified effects such as increased self-efficacy, changes in personality and mood and affect which all work together to increase motivation. Self-efficacy Figure 7. The effects of psychedelics in treated addiction (Adapted from Bogenschutz & Pommy, 2012) Bandura’s self-efficacy theory (1977, 1997) posits that a patient’s belief that they can control their substance-use (self-efficacy) and the belief cessation is "worth it" must be addressed before any treatment can work (Bogenschutz & Pommy, 2012). A review of the link between self-efficacy and addiction supports the strong link between a patient’s belief that they can recover and recovery outcomes (Kadin & Lit, 2011). Bogenschutz and Pommy (2012) hypothesise three ways that psychedelics help increase self-efficacy: Through mystical experiences, the patient may be more willing to make changes due to profound realisations that may occur during the psychedelic experience. Changes in personality can increase self-efficacy. Self-efficacy has been associated with certain personality dimensions (Conscientiousness, Extraversion, and Agreeableness). It is hypothesised that psychedelics can change certain personality dimensions, and thus increase self-efficacy. An increased mood due to psychedelic effects on the serotoninergic system could allow one to have a more positive outlook on life. Personality Although the idea of an "addictive personality" has not been supported by researchers, research on personality and addiction has shown that those who live with addiction tend to have certain personality dimensions from the Five-factor Model (FFM) including increased Neuroticism and decreased Conscientiousness and Agreeableness (Malouff et al., 2007). Early research conducted by McGlothlin et al. (1967) found that psychedelics can cause changes in personality. In this study, 58% of participants reported significant changes in their personality after taking LSD. These significant personality changes included improved assertiveness and interpersonal confidence. A more recent study by Maclean and colleagues (2011) supported this hypothesis, finding that after a single session of psilocybin, participants scored higher on the dimension of Openness. Futhermore, a review by Bouso et al. (2018) shows that psychedelic use is strongly associated with personality change in a range of different personality dimensions and traits including optimism and Openness. Mood and affect Studies have shown that psychedelic use has been associated with long-term mood and affect improvement. Studies conducted by Griffith and colleagues (2006, 2008) have supported this notion, with studies showing that participants in the psilocybin group reported greater positive mood compared to the control groups; these mood improvements in the psilocybin group remained significant during a 14-month follow up. In addition, a population study conducted by Hendricks et al. (2015) found that those who reported previous psychedelic use had decreased levels of suicidality and psychological distress compared to the general population. The positive and long-lasting effects of psychedelics on mood has important implications for addiction since the link between substance-use disorders and mood has been established (Bogenschutz & Pommy, 2012).   Bogenschutz and Pommy (2012) hypothesise that the effect of psychedelics on mood can affect addiction by: Based on the self-medication hypothesis of addiction (Khantzian, 1997; posits that individuals use drugs to relieve painful or negative affective), it is possible that a positive mood and affect (as a result of psychedelic use) removes the need to self-medicate to improve mood and therefore, reducing the need to "use" altogether. As negative affective states have been shown to be a risk factor of relapse (Kelly, et al., 2010; Hendershot, et al., 2011), it is hypothesised that improved mood and affect (as a result of psychedelic use) reduces the risk of relapse. Psychological effects and motivation Self-efficacy, personality, and mood all work together to improve a crucial part of rehabilitation: motivation (see Figure 7). Bogenschutz and Pommy (2012) hypothesised that profound and mystical experiences when taking psychedelics can improve one’s motivation to change by an interaction between increased self-efficacy, changes in personality, and improved mood/affect. Some people have addictive personalities and are therefore more prone to developing an addiction: True False How do psychedelics help an individual feel more motivated to change? Through: increased self-efficacy, improved mood, and personality changes changes in one's personality changes in behaviour changes in the environment Problems with using psychedelics and future research Although the research on using psychedelics for addiction seems overwhelmingly positive, it is not without limitations. Firstly, the studies on the effect of psychedelics and addiction that were conducted in the 1950s and 1960s lacked the rigorous methodology that is required of clinical studies now. Now that research on psychedelics has resumed, only pilot studies are available. These studies show positive results, however, as sample sizes are extremely small, researchers are unable to generalise the results to the population. In order to show that psychedelics are, without a doubt, an effective and safe treatment option for addiction, more double-blind placebo trials with large sample sizes must be conducted. Moreover, it has not been agreed upon what the most appropriate dosage for therapy is, since different studies use different methods. Research on psychedelics still has a long way to go to identify a "safe-threshold" of psychedelic dosage and thus, before it can be used as a therapy, a safe-dosage must be established to prevent any negative outcomes. It is important that the physiological effects of psychedelics on humans is established as it enables researchers to identify any potential risks of psychedelics. Finally, it is possible that psychedelics can act as a catalyst for other mental disorders. Due to the subjective nature of the "trip", the clinician is unable to predict if a patient will experience a "bad trip" and what the implications of a bad trip will be. There are many anecdotes from people who have developed mental illnesses due to bad psychedelic experiences. Unfortunately, not much research has been conducted on the topic. Like with all drugs, side effects are possible, so it is important to know what these risks are and how to deal with them to prevent adverse outcomes before prescribing psychedelic treatment. Conclusion Psychedelics, namely the classic psychedelics, are an extremely promising emerging treatment option for addiction. Research in this field since the 1950s has consistently shown that individuals treated with psychedelics have better outcomes than their controls. Psychedelics are able to increase motivation to get better through a complex interaction between physiological effects and psychological effects such as increasing self-efficacy, improving mood and affect, as well as making minor changes to personality traits/dimensions. Research in this field is growing and, in time, there is hope that psychedelics will become an approved treatment for addiction, however the research still has a long way to go. 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