Motivation and emotion/Book/2019/Psychedelic drugs and emotion

Overview


""It is important to expect nothing, to take every experience, including the negative ones, as merely steps on the path, and to proceed." - Ram Dass"

These famous words, one of the most famous quotes by Ram Dass who is a former academic and clinical psychologist from the Harvard University, formerly known as Dr. Richard Alpert. He went on to extensively research the therapeutic effects of psychedelic drugs and later experiment with the substances personally with his research partner, Timothy Leary in 1960. Ultimately carving the way for the legal research of psychedelic drugs.

The focus of this chapter is to discuss and examine the interactions between psychedelic drugs and our emotions. This chapter examines the historical, cultural, psychological and psychophysiological view upon the therapeutic use of psychedelics. How they affect our emotions, and potentially more importantly in the context of psychedelic therapy, how our emotions affect the psychedelic experiences.


 * Focus questions:
 * 1) How can we apply theories of emotion upon the emotional effects and characteristics of psychoactive/psychedelic substances?
 * 2) How can we measure the emotional effects of psychedelic drugs due to the subjective nature of the experiences?
 * 3) How do the emotional states people are in prior to, affect the psychedelic experiences?

Psychedelic drugs
Psychedelics are a group-classification of psychoactive substances which at higher doses, elicit visual, auditory, sensory and mental hallucinations. The most common class of psychoactive substances, classical psychedelics (psychedelic drugs that affect the serotonin receptors) include Lysergic Acid Diethylamide (LSD), Psilocybin, and Dimethyltryptamine (DMT).

The origins of use of psychedelic substances have been traced to BC times across almost all prehistoric societies and cultures across the world (Guerra-Doce, 2015). As a more concrete example, a fossil of a psychoactive cactus, Peyote, was dated to 6200-6800 BC (Guerra-Doce, 2015).

Emotion
Due to the subjectivity of emotion, it becomes very difficult to define in simple terms. Luckily, there have been many theories around this area that allow for the categorisation of many different feelings and emotions. In 1980, a major contributing theorist, Robert Plutchik, proposed the 'Wheel of Emotions' (Plutchik, 1980). Plutchik (1980) theorised through a diagram (see Figure 1.), that there were 8 basic emotions: joy, trust, fear, surprise, sadness, disgust, anger, and anticipation and 24 other primary, secondary and tertiary feeling and emotions.

Another major theory for emotion, proposed by William James and Carl Lange; The James-Lang theory hypothesised that emotions are a result of a physiological response to internal or external stimuli (Cannon, 1987).

Neuroreceptors


Various neuroreceptors are greatly involved in understanding the short-term, long-term, emotional and psychological effects of psychedelic drugs.

Serotonin
Serotonin (5-HT) is a major neurotransmitter responsible for the regulation of mood, appetite, digestion, the parasympathetic nervous system, memory, and sexual desire (De-Vernejoul, Collet & Chabbi-Achengli, 2012). Serotonin was first discovered in 1948 by Maurice M. Rapport, Arda Green, and Irvine Page of the Cleveland Clinic (Whitaker-Azmitia, 1999). This discovery ultimately led to the assumption that psychedelic drugs may act upon various serotonergic receptors, leading to an emergence in research.

The most common psychedelics; Lysergic acid diethylamide (LSD), Mescaline, Psilocin and N,N-Dimethyltryptamine (DMT) have been seen to strongly affect the serotonergic system, such that they are known as serotonergic psychedelics (Bouso, dos Santos, Alcázar-Córcoles & Hallak, 2018). Although there are upwards of 100 serotonergic psychedelics, this article will focus on the aforementioned four.

Significance of the 5-HT2A serotonin receptor
The 5-hydroxytryptamine(5-HT2A) otherwise known as the serotonin 2A receptor, is a sub-type of serotonin, primary to the psychological and biological effects of serotonergic psychedelics (Kraehenmann et al., 2017; López-Giménez & González-Maeso, 2017). The 5-HT2A receptor has been primarily found to affect the central nervous system (CNS). Furthermore, serotonergic psychedelics have been found to act as agonists upon many of the serotonin receptors, particularly the 5-HT2A (Serotonin 2A) receptor (Swanson, 2018). Researchers speculate that the agonistic effects brought on by various serotonergic psychedelics cause a reaction and activation of the visual cortex, resulting in various hallucinations (López-Giménez & González-Maeso, 2017).

However, a major aspect required to be researched further is the source of what causes auditory, sensory and olfactory hallucinations. There are minor theories which state that each basic sense; auditory, sensory and olfactory would be respective to their relevant cortex and the agonist's location. Due to the subjective nature of these hallucinations, they would cause an emotional reaction, potentially measurable by Plutchik's scale of emotions (Zamberlan et al., 2018; Griffiths, Hurwitz, Davis, Johnson & Jesse, 2019).

Dopamine


Dopamine (DA) is another major neurotransmitter that is majorly responsible for the communication between neurons in the nervous system, however, it is more commonly known for being the 'reward' neurotransmitter responsible for the positive feelings of stimulant drugs (Nestler, Hyman & Malenka, 2001). Dopamine was first discovered and reported in 1957 by Dr. Arvid Carlsson whilst on a search for the cause and treatment of Parkinson's disease (Yeragani, Tancer, Chokka & Baker, 2010). Additionally, the doctor found a way to measure the amount of dopamine present in the brain, finding that the highest concentration was in the basal ganglia (Yeragani, Tancer, Chokka & Baker, 2010). The basal ganglia is a significant contributor to decision making, motivation and working memory and there is an evident high concentration of dopaminergic receptor. This suggests that LSD and various dopaminergic partial agonists affect decision making, motivation and working memory, however more research is required (Giacomelli, Palmery, Romanelli, Cheng & Silvestrini, 1998).

Although dopamine is largely known to be responsible for the effects of various stimulants such as cocaine, methamphetamine and phencyclidine (PCP), it also has a significant role in the various unpredictable effects of psychedelics. As observed in previous studies, LSD functions as a partial agonist upon various dopamine receptors, particularly the D2 dopamine receptor (D2R) (Ahn & Makman, 1979; Giacomelli, Palmery, Romanelli, Cheng & Silvestrini, 1998). This suggests that although the substance is known to have adverse effects, the agonistic properties upon the D2 dopamine receptor may attribute to the feelings of great pleasure and 'transcendence', as reported by patients.

Quiz 1
{What are the three major serotonergic psychedelics? - LSD, MDMA, Mescaline + LSD, Psilocybin, DMT - MDMA, LSD, Marijuana - Psilocybin, Ayahuasca, Mescaline
 * type=""}

Psychedelics
As a result of the varying subjective hallucinations experienced under the effects of psychedelics, many short-term effects and changes (directly after the psychedelic experience) can be seen through the results of various studies (Bouso et al., 2015). Contrastly, long-term effects can be partly linked and attributed to increases in neural plasticity (Bouso et al., 2015).

Short-term effects
Psychedelics, including LSD, psilocybin and DMT have been found to function as partial agonists upon various serotonin and dopamine receptors (5-HT1A, 5-HT2A, D2R). Due to the complexity and strong differences in effects between psychedelics, it is very difficult to generalise the effects of the psychedelic-grouping. However, classic psychedelics are reported to cause altered states of consciousness, hallucinations (visual, auditory, sensory, olfactory) and ego-dissolution at higher doses (Sweat, Bates & Hendricks, 2016). In addition, psychedelics and more specifically, psilocybin, has been noted to alter and 'slow' the subjective experience of time, accompanied by increased reports of depersonalisation, leading to ego-dissolution (Wittmann et al., 2006).

Long-term effects
Due to the acute nature of psychedelic experiences, there is great potential for both positive and negative, long-term emotional and psychological effects. There have been several studies that have examined the effects of serotonergic psychedelics in contrast to individual psychedelics. As with the process of investigating the short-term effects of psychedelic drugs, psychedelics are too large of a classification of psychoactive substances to generalise effects for.

During the 21st century, many studies have been conducted, investigating the long-term effects of various psychedelic drugs. Most commonly, examining Ayahuasca/DMT, LSD and psilocybin. The findings from various studies showed through the use of follow-up interviews and questionnaires, no persisting perception disorders, psychosis or any negative effects from the therapeutic administration of psychedelics to healthy individuals (Bouso et al., 2015; McWilliams & Tuttle, 1973; Studerus, Kometer, Hasler & Vollenweider, 2010). Alternatively, researchers, MacLean, Johnson & Griffiths, (2011) concluded that 'mystical experiences' experienced through the use of psilocybin resulted in a long-term increase in the personality trait, openness. Furthermore, openness stayed significantly higher than baseline for over 12 months after the experimental session (MacLean, Johnson & Griffiths, 2011).

In 2016, a systematic review of clinical studies conducted in the previous 25 years investigated anti-depressive and anti-addictive effects of LSD, psilocybin and ayahuasca (Dos Santos et al., 2016). The findings revealed that the three aforementioned psychedelics showed greatly beneficial effects for anxiety, depression and assisted in the treatment of drug and alcohol addiction (Dos Santos et al., 2016). This finding suggests that serotonergic psychedelics can greatly assist in the treatment of various psychiatric disorders, however due to the small sample size of many of these studies, more research is required to attempt to replicate these findings (Dos Santos et al., 2016).

Set and setting
Many researchers have investigated the importance of 'set and setting', set reflecting the individual's mind-set, and setting being the environment. This term was originally coined by Timothy Leary in 1961, however, it has continued to be used and researched. Hartogsohn (2017) investigated the importance of set and setting through reviewing the pre-existing literature. The researcher concluded that the concept is crucial for both maintaining a safe, optimal psychedelic experience, allowing for the advancement of psychedelic research and also in general for drug research (Hartogsohn, 2017).

Neural plasticity
Psychedelics have been found to highly assist in the treatment of various mental and emotional disorders, especially psilocybin (Idell et al., 2017; Ly et al., 2018). Upon multiple examinations from various studies, brain derived neurotrophic factor (BDNF) levels appeared to increase upon the consumption of psilocybin suggesting that the substance assists with neural plasticity (Idell et al., 2017; Ly et al., 2018; Patra, 2017). BDNF is a gene that assists in the production and survival of neurons, and ultimately assisting in homeostasis (BDNF gene, 2019). Furthermore, the encouragement of plasticity suggests that these substances, alongside various psychological therapy can assist in the treatment of particular mental disorders.

Emotional effects of microdosing
The recent phenomena of 'microdosing' various psychedelics, most commonly, LSD and psilocybin has began to be researched. A recent systematic dual-study examined the effects of microdosing psychedelics in relation to long-term psychological well-being (Polito & Stevenson, 2019). In the first study, through the use of self-reported daily ratings from 98 microdosing participants and the implementation of pre and post study analyses, the researchers found that there were strong significant decreases in levels of depression stress, increased absorption and neuroticism (Polito & Stevenson, 2019). In the second study, 263 experienced microdosing patients participated in a very similarly designed observational study, he researchers found that directly after the microdose administration, a short-term boost across a range of psychological parameters occurred, however these were not sustained for longer than three days.

However, the researchers found that the expectancy bias was unrelated to the observed pattern of reported daily ratings (Polito & Stevenson, 2019). This study shows great potential for future research regarding the microdosing of psychedelics to assist with coping of various psychological disorders as a healthier alternative to pharmaceutical medications.

Quiz 2
{What are two of the long-term effects of psychedelics? - Increase in BDNF levels & Increase in depressive symptoms - Increase in conscientiousness & Increase in anxiety levels + Increase in BDNF levels & Decrease in depression and anxiety levels - Development of addictive symptoms & Decrease in neural plasticity
 * type=""}

Theories upon the emotional effects of psychedelic drugs


Due to the varying of complex emotional effects elicited during psychedelic experiences, identifying relevant psychological theories of emotion can be challenging.

James-Lange theory of emotions
Potentially, the most famous and earliest theory of emotion, produced by William James and Carl Lange in the 1890s; the James-Lange theory of emotions states that emotions are a reaction to a external stimulus, See Figure 4. This is consistent with the effects of various psychedelics, as it is a stimuli (as basic of one as a change in music) can cause a powerful positive or negative change in emotional well-being. James' view was that emotions originate from the perception of bodily states (Pollatos, Kirsch & Schandry, 2005; Wassmann, 2010). Although slightly outdated, the James-Lange theory stands as a postulase, functional theory of emotion.

Higher-order theory of emotional consciousness
A much newer theory hypothesised by LeDoux & Brown, (2017) views consciousness as a subjective experience, such that to attempt to separate the what it would be like to not be sentient the way we are as humans. As LeDoux & Brown, (2017) suggest, a major principle of the theory is that to experience consciousness, one must have a minimal inner awareness of their own ongoing mental functioning. Although, higher-order theory of emotional consciousness arose from a philosophical theory, it stands as a psychological theory and additionally, greatly aligns with higher-dose psychedelic experiences in relation to inner awareness of mental functioning (LeDoux & Brown, 2017). Subjective reports of psilocybin, LSD, and DMT experiences revealed that at higher doses, strong dysphoria, anxiety and panic was noted due to increased 'self awareness' (Studerus, Kometer, Hasler & Vollenweider, 2010; Griffiths, Hurwitz, Davis, Johnson & Jesse, 2019). This finding fits well within the theory, suggesting that at higher doses, a individual would experience a higher level of inner-awareness and potentially feel discomfort as a result.

The broaden and build theory of positive emotions
Lastly, the broaden-and-build theory of positive emotions, developed by Fredrickson, (2004), a staple theory of emotion in positive psychology states positive emotion (enjoyment, happiness) broadens an individual's perspective and self-awareness. The broaden and build theory is consistent with subjectively reported 'transcendental' experiences elicited by classic psychedelics; LSD, psilocybin and DMT (Fredrickson, 2004; Griffiths, Hurwitz, Davis, Johnson & Jesse, 2019). In Griffiths, Hurwitz, Davis, Johnson & Jesse (2019), after having 'trascendental/mystical' experiences, more than two-thirds of the participants rated the experience as among the most personally meaningful and spiritual of their lives. Although, limited in sample size and generalisability, these findings reinforce Fredrickson's proposal of positive emotion, ultimately broadening an individual's perspective and awareness (Fredrickson, 2004).

Psychedelic Therapy
As of the recent re-emergence of the study of psychedelic substances there has been much research suggesting the positive effects of psychotherapy whilst undergoing a psychedelic experience.

LSD-assisted psychotherapy
In a recent study, Gasser et al., (2014) investigated the potential for LSD-assisted psychotherapy for anxiety treatment with those with a life-threatening disease. Initially, the researchers administered 200µg of LSD to the first group, and 20µg to the second with a cross over to a dosage 200µg after the initial treatment session (Gasser et al., 2014). Alongside the psychedelic experience, psychotherapy was supplemented, as well as drug-free psychotherapy sessions for 2-3 weeks post experience (Gasser et al., 2014). 2-months post ‘trip’ during a follow-up, with use of the State-Trait Anxiety Inventory (STAI), positive changes were noted, specifically in the reduction of state and trait anxiety (Gasser et al., 2014). The findings from this study in particular suggest that LSD has great potential in the use of anxiety reduction under therapeutic supervision, however, more research is required to confirm this claim (Gasser et al., 2014).

MDMA-assisted psychotherapy
Alternatively, 3,4-methylenedioxymethamphetamine (MDMA), a synthesised psychoactive stimulant/psychedelic has been heavily researched for therapeutic potential, alongside other aforementioned serotonergic psychedelics.

One study in particular, conducted by Mithoefer et al., (2019) examined MDMA-supplemented psychotherapy as a treatment for post-traumatic stress disorder (PTSD). The active group received (either of two active doses of MDMA – 75 or 125mg) while the control group received placebo doses whilst undergoing psychotherapy (Mithoefer et al., 2019). Results revealed that strong significant symptom reductions were noted in the active group who received active doses of MDMA accompanied by psychotherapy (Mithoefer et al., 2019). Although the placebo effect did also have a significant effect, the effect size was very minor (half of the active group), suggesting that MDMA greatly assisted in the administration of psychotherapy and treatment (Mithoefer et al., 2019).

Psilocybin-assisted psychotherapy
Several studies have examined the potential of psilocybin for therapeutic use of various mental disorders, including depression and anxiety (Schenberg, 2018). Ross et al., (2016) investigated the efficacy of psilocybin upon treating anxiety and depression upon a sample of individuals with life-threatening cancer. With use of a double-blind study, the researchers randomly assigned participants to either an active (receiving 0.3mg per kg of psilocybin) or placebo/control group with conjunction to psychotherapy (Ross et al., 2016). The results showed that psilocybin-assisted psychotherapy showed major decreases in anxiety and depression levels, alongside lower levels of demoralisation and hopelessness (Ross et al., 2016). Alongside the results of other psychedelic assisted psychotherapy, psilocybin appears to greatly assist in the treatment of anxiety and depression.

Ayahuasca and DMT-assisted psychotherapy
N-dimethyltryptamine (DMT) and ayahuasca has been researched to a very miniscule amount in comparison to the aforementioned psychedelics. However, the studies that have been conducted show promising results. Thomas, Lucas, Capler, Tupper and Martin, (2013) researched the efficacy of ayahuasca-assisted psychotherapy for addiction, through the use of pre-and post-treatment measurements. The results suggested a significant improvement in mindfulness and quality of life, in addition to self-reported reduction in alcohol, tobacco and cocaine use (Thomas et al., 2013). Through the use of a follow-up, six months after the study, participants seemed to have experienced lasting positive emotional and psychological changes (Thomas et al., 2013). Although the results of the study show great promise, more research needs to be conducted to further understand the mechanisms of ayahuasca and N, N-dimethyltryptamine, and its use in the treatment of addiction and disorders.

Conclusion
Psychedelics are psychoactive substances that can elicit visual, auditory, olfactory and sensory hallucinations. These hallucinations can be attributed to partial agonistic properties of psychedelics upon various neuroreceptors. As a result, psychedelics can greatly affect emotional states and overall well-being, in both short and long-term. Through the use of microdosing, psychedelics have been noted to be more controlled and beneficially to the treatment of addiction and mental health, although more research needs to be done to understand this phenomena. However, due to the complex legal bindings for psychedelic drugs, the only existing studies are funded privately, with no government funding assisting towards research costs. In relation to various psychological literature and theories of emotion, psychedelics can be interpreted through various theories, suggesting a point in direction for research. In addition, many serotonergic psychedelics are being used alongside psychotherapy to treat various psychological disorders, including depression, anxiety, PTSD and addictive disorders.