Therapeutic Use of Street Drug

Therapeutic Use of Street Drug

In December 24 of 1912, G. Mannish and W. Jacobsohn, two chemists under the German pharmaceutical giant, Merck, filed a patent for a vasoconstrictor[K1] known as hydrastinine along with its chemical intermediates (E. Merck, 2006). However, one of the said chemical intermediates[K2]served many different purposes. In the 1950s, the American military used it as a ‘truth serum' while It wasn’t until the 1960s that this chemical intermediate was rediscovered by a man named Alexander Shulgin who introduced this substance to a close group of friends. [K3] in 1977, the substance was introduced to a psychologist by the name of Leo Zoff, who took interest in its potential for therapeutic purposes.As a therapeutic drug, it developed a reputation for enhancing communication during clinical sessions, reducing patients’ psychological defenses, and increasing capacity for therapeutic introspection. As time progressed however, this drug found its way into the hands of the public and became widely abused as a recreational drug, becoming an integral element of the rave culture and clubs.Eventually, it becameone of the most widely illicit drugs in the United States (Turner, 1998). On March 23, 1988, 3,4-methylenedioxy-N-methylamphetamine (MDMA) was permanently declared a Schedule I drug because of its high potential for abuse (MDMA, n.d.).

Pure MDMA is a white crystalline solid not found in nature, but rather synthesized from safrole, a colorless or slightly yellow oily liquid that is extracted from the root-bark or the fruit of the sassafras tree. It is a chemically stable compound that does not decompose easily in air, light, or heat. It will dissolve in water but does not absorb the dampness from the air. In addition, MDMA is a chiral molecule which means it has four different groups attached to one of the carbons and a mirror image of the molecule is not superimposable on the original. It is optically active and usually found as a racemic mixture yielding a 50-50 mixture of the R and S enantiomers. The S-enantiomer has a shorter elimination half-life and a greater excretion than the R-enantiomer (Saunders, 2012).

Although there are a number of methods to convert safrole into MDMA using different intermediates, the most common is through a3,4-methylenedioxyphenyl-2-propanone (MDP2P), also known as apiperonyl acetone, intermediate. There are two ways to synthesize this compound. The first method involvesisomerizingsafrole to isosafrole in the presence of a strong base, and then oxidizing thatisosafrole to MDP2P. The other method makes use of the Wacker process to oxidize safrole directly to the MDP2P intermediate by means of a palladium catalyst. Once the MDP2P intermediate is prepared, a reductive animation leads to MDMA (MDMA, n.d.).Below figure from (Synthesis: How your favorite drug was probably born., n.d.).[K4]

MDMA is most often available in tablet form to be ingested orally although it can be available as a powder and snorted, occasionally smoked, and (rarely) injected (MDMA- Consumer Information, n.d.). The drug is a synthetic, psychoactive drug that can induce a state of euphoria, stimulation, as well as distortions in time and perception and an enhanced enjoyment from tactile experiences. MDMA essentially acts as a releasing agent of serotonin, norepinephrine, and dopamine- all of which are naturally occurring neurotransmitters. MDMA enters the neurons through its monoamine transporters. Once inside, MDMA inhibits the vesicular monoamine transporter, which in turn stimulates the release of serotonin, norepinephrine, and dopamine in the brain by reversing their respective transporters via phosphorylation (MDMA, n.d.). In other words, MDMA instigates the release of specific neurotransmitters whilst blocking the reuptake mechanism by the synaptic terminal that released it. The effects as a result of this mechanism are felt anywhere from a half hour to an hour after consumption. Within that time, a peak high is produced that lasts around 2 hours, after which the high plateaus and lasts about 3.5 hours. This high is followed by what is known as a ‘comedown’ or withdrawal of the euphoric symptoms for several hours. During this period of time, the user ironically feels unhappy and fatigued.

There are a number of adverse effects associated with MDMA. Top side effects include difficulty concentrating, grinding of teeth during sleep, lack of appetite, and dry mouth/thirst. In addition, short term health concerns include dehydration, hyperthermia, and hypothermia. This is largely attributed to the stimulant nature of the drug.A person undergoing continuous activity without sufficient rest and excess loss of fluid via perspiration could put a user at risk. Furthermore, long term effects can include a reduction in the reuptake concentration of serotonin transporters in the brain. An increased rate of depression and anxiety, even after quitting the drug, can occur due to the damage of serotonin neurons (MDMA, n.d.). Incidentally, the impact of neurotransmitters is lowered and more MDMA is needed to achieve the same effect which can lead to an addictive cycle.

Several users of the drug use the terms MDMA and ecstasy (among other nicknames) interchangeably. This is, despite what users believe, a misconception in and of itself. MDMA is 3,4-methylenedioxy-N-methylamphetamine and works on specific neurotransmitters as discussed previously. Ecstasy however, is the street name for MDMA and in fact, generally, does not contain pure MDMA. Drug manufacturers will often produce different types of ecstasy pills with ‘nicknames’ using colors and popular terms. What most people don’t realize is that the street drug ecstasy is seldom MDMA- in fact, 13% of the ecstasy seized in New York by the DEA in the last 4 years contained any MDMA at all. Even then, it was mixed with several other drugs (Drew Griffin, 2013). In other words, most people have no idea what they are actually taking. Unlike pure MDMA that have known effects on the body and a history of specific usage and research, the formulas for the street drug ecstasy is constantly changing and aren’t tested. The mix of chemicals in the street drug can have unexpected consequences and can lead to serious physiological problems or even death.

Despite all the usage, addiction, and abuse of MDMA, there is research being done on the therapeutic potential of the drug. Clinical trials results in the Journal of Psychopharmacology suggests that MDMA can be administered to subjects with Post Traumatic Stress Disorder (PTSD) without evidence of harm. The drug reduces fear responses wherein psychotherapy can actually take effect. Participants that were treated with a combination of MDMA and psychotherapy clinically and statistically significant improvements in their PTSD. Most medications for mental illnesses are often taken daily for years, sometimes forever. On the other hand, MDMA is only administered a few times before psychotherapy to reduce fear and increase trust without inhibiting painful emotions. This is due to the release of serotonin, among other minor neurotransmitters including oxytocin, prolactin, and cortisol (MDMA (Ecstasy)-assisted psychotherapy relieves treatment-resistant PTSD, study suggests, 2010).

The participants in the study were required to have received and failed to obtain relief from both psychotherapy and psychopharmacology. Over 80% of the trial group no longer met the criteria for PTSD in the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) following the trial compared to the 25% of the placebo group. With such successful preliminary results for the treatment of PTSD, there is a good possibility that other psychological disorders can become overcome with MDMA and psychotherapy. The downside to this treatment is that if MDMA-based treatment became acceptable, there would have to be special clinics equipped for long treatment sessions (MDMA (Ecstasy)-assisted psychotherapy relieves treatment-resistant PTSD, study suggests, 2010).Subsequently, there would have to be a tighter regulation on the manufacturing of the drug and abuseof the drug may become an even bigger problem than it is now.

Even though MDMA has shown to offer therapeutic effects, further in depth studies of the effects of MDMA on the brain was necessary to fully address the issue of whether or not MDMA causes cognitive decline. After much research and drug tests, it was concluded that MDMA indeed does not harm the brain. To ensure the accuracy of the tests, The National Institute on Drug Abuse eliminated external potential factors that could lead to mental impairment including sleep deprivation, previous drug or alcohol use, and former cognitive damage (No Brain Damage From Ecstasy, New Research Shows, 2011). Using these factors to screen subjects via drug tests using hair samples and other methods, researchers have determined that it does not create holes in your brain or directly cause cognitive decline. However, it is still highly addictive and in some cases, can lead to fatalities.

In the United States, MDMA was legal and unregulated until it became used recreationally in the 1980s. During this time, it became classified as a Schedule 1 drug. During DEA hearings, several experts and psychologists recommended MDMA to be reclassified as a Schedule 3 drug, due to its beneficial usage in psychotherapy. For a short time, MDMA was reclassified as a Schedule 3 drug in 1987 but in 1988 was once again reclassified as a Schedule 1 drug and has been there since (MDMA, n.d.).

MDMA has its benefits but also its drawbacks. The current usage of MDMA exists majorly as a club drug that is taken liberally by frequent users. Despite being a Schedule 1 drug, thereby classified as high potential for abuse and having no current accepted medical use by the DEA, there is an extremely high demand for the drug and it continues to circulate the rave scene. As such, there are several risks associated with MDMA, even death. It should be noted however, that there does appear to still be potential usage for MDMA in a therapeutic setting. It will be interesting to see the future of the drug and if the Schedule 1 ruling will ever be reverted to Schedule 3. If MDMA does become classified as a Schedule 3 drug, it may even be safer due to the regulation of its synthesis and its availability in its purest form. In addition, this could help those with mental disorders that have no alternatives. However, the potential for abuse may outweigh the necessity for a new form of psychotherapy.

Bibliography

Drew Griffin, N. B. (2013, November 23). 9 things everyone should know about the drug Molly. Retrieved from CNN:

E. Merck. (2006). Retrieved from mdma:

In the Beginning... (n.d.). Retrieved from TheDEA:

MDMA. (n.d.). Retrieved from Wikipedia:

MDMA (Ecstasy)-assisted psychotherapy relieves treatment-resistant PTSD, study suggests. (2010, July 20). Retrieved from ScienceDaily:

MDMA- Consumer Information. (n.d.). Retrieved from Drugs:

No Brain Damage From Ecstasy, New Research Shows. (2011, 5 25). Retrieved from HuffingtonPost:

Synthesis: How your favorite drug was probably born. (n.d.). Retrieved from TheDEA:

Turner, E. J. (1998). Ecstasy's History. Retrieved from

[K1]perhaps you could define what a "vasoconstrictor" is

[K2]what is this intermediate? what is its structure?

[K3]I think this could be omitted

[K4]you should mention which method does the figure below represent or you can provide a mechanism for each method