Motivation and emotion/Book/2015/MDMA and psychotherapy

Overview
3, 4-MethyleneDioxy-MethAmphetamine or more commonly known as 'MDMA' is a well known substance widely associated with its positive social effects on the brain. For the last sixty years MDMA has been in question about its effectiveness in conjunction with psychotherapy and this book chapter explains an overview of the substance and the beneficial aspects of MDMA-Assisted psychotherapy.

MDMA, in conjunction with psychotherapy, has seen positive effects on many patients including those with Post Traumatic Stress disorder (PTSD). Although it is still up for debate on whether its effectiveness outweighs the negative associations. Further research into this form of therapeutic healing is needed to expand the knowledge of individuals and to break the negative stigma held on MDMA. The introduction of MDMA-Assisted psychotherapy into the modern psychotherapeutic world could improve the lives of many individuals suffering from psychiatric illnesses and change the way therapy is seen today.

What is MDMA?
MDMA is a psychoactive chemical substance that has biological effects on the brain and the body. The scientific name is known as 3, 4-MethyleneDioxy-MethAmphetamine (MDMA) and it is classified as an illegal schedule 1 drug. The substance produces both a stimulant and on occasion hallucinogenic effect on the brain. The main effects cause alternations to thinking, perception and consciousness. MDMA is now a popular recreational party drug and is also referred to as the hug drug, disco biscuit and ADAM.

How does MDMA work?
MDMA works by increasing the activity in the brain and by altering the chemistry of three neurotransmitters; Serotonin, Dopamine and Norepinephrine (Drugabuse.gov). After ingestion, MDMA is rapidly absorbed into the bloodstream and once it reaches the brain the effects can start immediately. After absorption, MDMA binds to the serotonin transporters and enhances the release of serotonin and the inhibition of serotonin re-uptake by serogentic nerve endings (Pubchem.ncbi.nlm.nih.gov, 2015). This triggers the release of an excess flow of serotonin, dopamine and norepinephrine into the blood stream, causing both physical and psychological effects. The excessive amounts of these neurotransmitters cause a release of hormones such as Oxytocin and Vasopressin (Drugabuse.gov). The increase of these neurotransmitter and hormones stimulates the 5-HT2 receptor in the brain, thus causing psychoactive effects to occur. The average dose of MDMA is around 70 to 80mg per dose (TheDEA.org, 2015). Additional doses can be taken by users whom are used to the effects and need a stronger amount, although it is not recommended to take more then two doses in one go.

The structure of MDMA
MDMA is a part of the phenethylamine family of drugs, which means that it is a “designed drug” which has both stimulant and hallucinogen effects on the brain. MDMA is classed as a mild central nervous system stimulant, empathogen (emotional relatedness and openness), mild hallucinogen and psychedelic (Emcdda.europa.eu, 2015).

The structure of MDMA is chemically similar to methamphetamine, as it has the same effect to a stimulant on the brain as methamphetamine would. This is where the psychoactive reaction comes from and this is the chemical part that provokes a change in the brain through increased sensitivity. MDMA is also chemically similar to Mescaline which is the psychedelic branch of the hallucinogen part of MDMA and this produces the increased awareness in the body. Although it contains hallucinogenic properties, it does not always produce those effects and varies between individuals.

Physical form
The most common form of MDMA is in the hydrochloride from of whitish crystals or powder that is soluble in water this is then place into a clear capsule for ingestion (Emcdda.europa.eu, 2015). MDMA is usually taken orally but when made into different physicals forms can be taken by injection and snorting.

Synthesis
MDMA has four principal precursors which can be used to produce the substance; safrole, isosafrole, piperonal and 3-4methylenedioxyphenyl-2-propanone (PMK) (Emcdda.europa.eu, 2015). Safrole is main key ingredient when production of MDMA. In the first production of MDMA, safrole was used to react with hydrobromic acid and this formed the chemical bromosafrole which was then mixed with methylamine and converted to MDMA (Emcdda.europa.eu, 2015). Different methods of producing the substance are now known and PMK is commonly used now in the manufacturing of MDMA. Almost all MDMA sold exists as a racemic mixture (Emcdda.europa.eu, 2015).

The effects of MDMA
After ingestion, MDMA can take 20 minutes to an hour to be absorbed, depending on the serviette of the dose. The effects can vary from mild to severe, positive and negative, immediate and lasting. MDMA temporarily alters the brain chemistry and causes the change in the regulation of mood, sleep and pain (Emcdda.europa.eu, 2015). The severity of the effects depends of individual susceptibility and the circumstances and environment in which the MDMA was taken in. (Maté, 2015). Each brains' circuitry system and chemistry reflects their experiences and this has a big influence on the effects of substances like MDMA (Maté, 2015).

Immediate physical effects
The immediate physical effects of MDMA can be dry mouth, mydriasis (dilated pupils), sweating, nausea, muscle tension, involuntary jaw clenching and teeth grinding, Nystagmus (eye muscle twitching) increased heart rate, and increased blood pressure (drugabuse.gov, 2015). The psychical effects are caused by the neurotransmitter and hormones engaging the parasympathetic nervous system (Dvorsky, 2015).

Psychological effects
MDMA is known for its psychological effects on the brain. The psychological effects of MDMA can be felt almost immediately after absorption and are very positive for the user. These effects can include increased energy, euphoria, emotional warmth, love, lust, trust and empathy towards others, increased self-awareness and sense of well-being, confidence, mental stimulation, relation, increased sociability and connectedness, dissolution of neurotic fear (TheDEA.org 2015), sexual arousal, and enhanced appreciation (drugabuse.gov). These effects are caused by the excessive amount of serotonin running through the bloodstream, creating an overall happiness and positive effect on the emotions of the user. The release of oxytocin and vasopressin into the bloodstream are hormones that produce and enhance feelings of love, lust, trust and sexual arousal. This what causes the increases of this feelings after taking MDMA (drugabuse.gov). The increased feelings of confidence are due to dopamine release which causes emotional positivity and enhances functioning.

Anything that chemically alters the brain can have negative side effects. This is due to the individual brain chemistry and how the effects can be subjective to each individual brain. Negative effects from MDMA can occur when the purity level is low and the substance is cut with other chemicals that can be dangerous to the brain and body. The negative effects can include paranoia, confusion, fatigue, sleep disturbances, attention dysfunction, irritability, thirst, lack of appetite, decreased fine motor skills and distortions in sensory perception (drugabuse.gov, 2015, TheDEA.org, 2015). As MDMA temporarily alters the brain chemistry, it may trigger, cause or worsen psychiatric problems for vulnerable individuals, although this is very uncommon (TheDEA.org, 2015).

Long-term effects
The longer term effects can start from the day after the substance is used and can last for a significant time depending on the severity of the dose and how long the individual has been using the substance for. These effects are usually the negative ones, and more likely to last from a day up to a week later, while the user is coming off/down from MDMA. These effects can include restlessness, irritability, thirst, sleep disturbances, lack of appetite, poor memory recall, sadness and reduced sexual drive (drugabuse.gov). These act as ‘hungover’ effects and vary on the dosage amount and the users' ability to process the substance

Long-term effects can be worse in heavy and repeated exposure and can cause mild to severe negative effects on the brain and body. This is due to the decrease in the tissue levels and damage of the receptor 5-HT2 causing a reduction in the natural serotonin release (Schenk, Abraham, Aronsen, Colussi-Mas & Do, 2013) This causes changes in the brain regions that control cognition, emotion and motor control and cause effects such as long lasting confusion and impairment of working memory (Schenk, Abraham, Aronsen, Colussi-Mas & Do, 2013).

Is MDMA addictive?
MDMA is not a physically addictive substance. as it does not contain addictive properties (Emcdda.europa.eu, 2015). The feelings and effects that an individual receives on MDMA can be addictive if they are not receiving those feelings from another stimulus (Maté, 2015). MDMA can be an emotional release from reality for some individuals and this can cause an addiction to form. This is usually happens in vulnerable individuals that lack the essential chemicals in the brain such as endorphins, dopamine and serotonin, the very substances that MDMA supply or enhance (Mat, 2015).

Scientific research has proven that emotional stress is a consistent trigger for addictive behaviour and the need for an external stimulus which causes dependance on substances (Maté, 2015). Individuals who have suffered trauma often become the victims of addiction especially with substances, as they provide the feelings they are searching for through the chemicals they release and enhance (Maté, 2015). As MDMA does release and enhance serotonin, addiction can for some individuals can occur that are looking for a void to fill. Individuals can and will get addicted to anything that provides those feelings which they are missing. This has little to do with the substance itself as it is just used as a means to receive these effects. If the substance MDMA was addictive, every individual who has ever tried it, would be an addict.

Toxicity
It is unusual for an individual to reach toxicity after taking MDMA, if the substances purity level is high and the user has a moderate dose. The reported cases of an MDMA overdose are rare and depends highly on the severity of the dose taken and the individual's susceptibility to the substance. Fatalities have been recorded from doses over 300mg which is roughly around 4-5 capsules, when the average dose is 70 to 80mg per capsule (TheDEA.org, 2015). An average of 20 deaths per year since 1990 have been recorded as MDMA-related (Sessa & Nutt, 2007).

The mislabelling of MDMA is common and an important aspect to think of when thinking of taking it. Ingesting a substance that is mislabeled is extremely dangerous as the chemicals are unknown and effects can be detrimental to the health of the user. MDMA is commonly cut with PMA (para-methoxyamphetamine) and this substance is known to be sold on the streets as MDMA (Gage, 2013). In low doses, PMA has similar effects on the brain to MDMA and can easily be mistaken, even in physical form and testing kits (Gage, 2013). However, PMA effects wear off quickly, making some individuals take additional does which can cause toxicity to happen and cause an increase in body temperature, raised blood pressure, increased heart rate, seizures and overdoses (Gage, 2013).

The manufacturing of MDMA after its illegal ban has still occurred however,  unfortunately this was not by chemists or professional who could accurately produce pure MDMA. This caused a spike in the occurrence of impure and incorrect synthesis of MDMA, resulting in toxic contaminants being added (Pentney, 2001). The negative effects were attributed to MDMA and are still associated with the substance.

History
The first sign of MDMA was found in a patent filed in 1912 by a German pharmaceutical company called Merck (Pentley, 2001). The substance was accidentally discovered from developing a precursor to a synthesis for a homeostasis substance which was hoped to be effective in controlling bleeding. This was called Methylsafryamin (Freudenmann, Öxler & Bernschneider-Reif, 2006). Although there is no evidence, Merck was not aware of its psychoactive properties and only marketed as it’s intended use (Freudenmann, Öxler & Bernschneider-Reif, 2006). The company then decided against the patent and dropped it, having nothing more to do with the substance (Pentley, 2001).

The substance remained untouched until 1953 when the US army contracted a study for the toxicity and behavioural effects of MDMA to be assessed (Pentley, 2001). MDMA was one of eight Edgewood Arsenal compounds to be chemically tested on animals (Pentley, 2001). The results showed no brain damage or neurotoxicity occurred from the ingestion of MDMA, although no more studies were conducted (Pentley, 2001).

In the 1970s, Dr Alexander Shilgin, an American pharmacologist rediscovered the substance and promoted MDMA as a therapeutic tool (Drugfoundation.org.nz, 2015). In 1976, Leo Zeff was the first psychotherapist to use MDMA as a treatment for psychiatric illnesses within psychotherapy sessions (Pentley, 2001). He performed over hundreds of sessions using MDMA as a therapeutic tool and referred to the substance as ADAM (which is still sometimes used today), although there were no publications from Zeff on these sessions (Pentley, 2001). MDMA became increasingly popular with psychotherapists as a strong relationship could be formed from the increase in communication that MDMA caused (pentley, 2001). MDMA was known by therapists as ‘penicillin for the soul’, due to its effectivenesses in psychotherapy (Drugfoundation.org.nz, 2015).

Despite its remarkable characteristics, in 1985, MDMA was banned by the Drug Enforcement Agency and was placed on the schedule 1 list of controlled substances (Drugfoundation.org.nz, 2015). The reasoning behind this was because it was deemed to have no therapeutic or medical beneficial use, a high potential for abuse and had a lack of safety for human consumption (Pentley, 2001). This decision was not in favour of many therapists and health care workers and multiple protests were organised to stop the ban from proceeding (Pentley, 2001). MDMA did not meet the criteria for an illicit drug and was referred to as a ‘hazard for public safety' (Pentley, 2001). The ban become permanent in 1988 in the US and was soon followed in other countries including Australia,and New Zealand, although in Switzerland in 1988 to 1993 MDMA was used as a legal prescription drug until it was later prohibited (Oehen, Traber, Widmer & Schnyder, 2012). MDMA still remains on the Schedule 1 listing (Pentley, 2001).

During the surge of MDMA in the 1970s, it became increasingly popular in social environments and party scenes. As individuals were becoming aware of the positive effects from psychotherapy sessions (Pentley, 2001). MDMA has continued its popularity despite its illegal ban, and it was estimated that in 2013 there were around 2900 thousands individuals who took MDMA around the world (Chawla, 2013). The consumption of MDMA has less therapeutical reasoning now and is used as a party drug and to enhance enjoyment for individuals. The most popular ages for MDMA occurs between ages of 18 to 25, and is usually used as an experimental experience (Pentley, 2001). The hype about MDMA is still current and consumption usually occurs after initial exposure to the substance (pentley, 2001).

MDMA as Psychedelic Medicine
MDMA has been a questionable substance since it was developed in the early 1900s and especially when it comes to psychedelic medicine and the use of it as a therapeutic tool. It has gained a reputation from its effects and is perceived both positively and negatively among many individuals.

Ultimately, the use of MDMA in conjunction with psychotherapy should not be compared to the use of MDMA in individual and social settings. The argument for and against MDMA has little evidence due to the bias in research by political and government owned agencies (Pentley, 2001). Thus, creating an unfair ground for MDMA as a therapeutical tool to stand on. MDMA’s temporary alteration of the brain's chemistry and enhancement of positive emotions makes it a reasonable and practical aid in the treatment of psychiatric illnesses. The positive effects that MDMA creates in the brain, such as feelings of trust, love, empathy and warmth towards others, give PTSD suffers a chance to openly talk about their traumas that once gave them anxiety and pain. MDMA increases neurotransmitters and hormones that allow individuals to remove mental barriers and diminish the fear response (Pentley, 2001). The use of this, along with psychotherapy sessions, can provide increased progression to positive outcomes.

This is especially helpful for individuals who suffer from Post Traumatic Stress Disorder (PTSD). Using MDMA in conjunction with a controlled psychotherapy environment, can decrease and help uncover psychological and emotional damage caused by PTSD (MAPS, 2015). MDMA-assisted psychotherapy works by shifting the attention of the patient towards more positive experiences and thoughts and limits the impact of negative feelings (Skomorowsk, 2015). When an individual takes MDMA their capacity to perceive negative emotions decreases and they cannot accurately process negative perceptions. The use of this for PTSD patient can dramatically help them in entering memories without the negative effects (Skomorowsk, 2015). This would allow for the individual to openly access and express their traumas and issues which will decrease the power of the trauma as the main techniques used within the sessions are exposure and desensitisation.

PTSD patients need to relive the distressing memories of the events for psychotherapy to work and when the patient takes MDMA, the distressing memories become less vivid and gives them a better insight into their issues and reduces their psychological defence (Skomorowsk, 2015). Not only is the substance beneficial on an individual level but the relationship between patient and therapist improves in MDMA-assisted therapy. The enchantment of feelings of trust and empathy towards others make the bond between the patient and therapist evolve, creating a safe environment for the patient with fear or anxiety.

In laboratory studies, from MAPS, pure MDMA has been proven safe for human consumption in moderate doses and in safe environments (MAPS, 2015). MDMA doses in conjunction with psychotherapy range from 50 to 150mg and are administered moderately with a maximum of three doses (Bouso, Doblin, Farré, Alcázar & Gómez-Jarabo, 2008 Pentley, 2001). When MDMA was given to healthy, stable individuals under controlled, medical settings and supervision, it has been recorded that the substance creates a euphoric mental state for every user, every time (Sessa & Nutt, 2007). The results of a study by Bouso, Doblin, Farré, Alcázar & Gómez-Jarabo (2008) revealed MDMA to be both psychologically and physiologically safe and effective for six women with PTSD whom which had failed to respond to previous treatment methods.

A study conducted by neurologists in London looked into the effectiveness of MDMA’s use in psychotherapy through fMRI responses to the best and worst autobiographical memories that 12 participants had (Skomorowsk, 2015). The participants were asked to recall six of their worst memories and six of their best memories when under a fMRI scanner (Skomorowsk, 2015). The study was conducted twice, when the participants were on MDMA and when the participants were not. After the use of MDMA, participants recalled their favourite memories as more emotionally intense and vivid and recalled their worst memories as less negatively vivid and intense (Skomorowsk, 2015). fMRI images revealed differential activation in the regions of the brain associated with positive and negative memories after taking MDMA and not (Skomorowsk, 2015). This study proves that MDMA causes individual to physically think differently about their memories and ascribe more positive feelings towards them.

Extended research needs to be aimed at the negative effects that may be caused by repeated exposure to MDMA and the effects on the substance on vulnerable individuals. The long-lasting effects of heavy MDMA use may be a concern for the therapeutic use of MDMA as it has been recorded to have negative effects in the serotonin receptors and decreased tissue levels in the brain. Although in 1990, Greer and Tolbert tested 80 patients with MDMA-Assisted psychotherapy and revealed that 90% of patients experienced lasting beneficial effects that remained after a year follow-up with no long lasting negative effects (Bouso, Doblin, Farré, Alcázar & Gómez-Jarabo, 2008). For MDMA-assisted therapy to gain effectiveness and credit, it must be made into a reliable, and pure drug that is made accurately by professional chemists. MAPS is currently undertaking a $20 million plan to make MDMA into an approved prescription medication by 2021 (MAPS, 2015). MAPS is the only organisation funding clinical MDMA trails on humans for medical and therapeutical use (MAPS, 2015).

Conclusion
MDMA is a safe substance that when used in moderation can have very positive effects on the users and be beneficial in social, and therapeutical situations. MDMA can be used as a tool to understand the human brain and to reveal ways to help individuals with psychiatric illnesses such at PTSD to live more effectively and have control over their lives and emotions. Like any substance that can alter the brain, negative effects need to be assessed in the definite safety of human consumption and be highly regulated. The research about MDMA-assisted psychotherapy is limited due to its legal stance and funding barriers by government funded agencies. The removal of MDMA from Schedule 1 will improve the attitudes and views of the substance and conceivably increase the likeliness of MDMA becoming legal in conjunction with psychotherapy sessions, ultimately leading to a reduction in PTSD and other psychiatric illnesses that control many individual's lives. This kind of advancement in therapy could help to improve the emotional lives of those affected and those associated with  suffers. Having the ability and chance to help change the lives of people in need is what should be in focus.