Ecstasy Designer Drug 2C-E and a Death in Oklahoma

Chemical Structure 2C-E

If you are a parent of a teenager I hope you took chemistry in high school or college because you are going to need it.  The reason you are going to need it is the emergence of designer drugs of abuse.  Designer drugs typically have a parent compound that is chemically modified.  There are two key reasons to modify existing illegal compounds: 1.) the new compound may not be illegal until state and federals laws can be modified and 2.) the new compound may have potent psychoactive effects.

Unfortunately, some effects of the designer drugs may not be so beneficial.  A young adult Oklahoma woman died recently after ingesting a designer drug known as 2C-E.  Additionally, seven young adults at the same party were hospitalized for adverse effects. 

The number and type of designer drugs is pretty extensive.  The parent compounds for some of these designer drugs include marijuana (tetrahydrocannabinol), ecstasy (MDMA), PCP and the opiate drug fentanyl.  2C-E is a designer drug derived from phenethylamine.

Deaths due to ecstasy use are uncommon.  Many deaths in ecstasy users occur in the context of alcohol and other drug use making the specific contribution from ecstasy unclear.  MDMA may contribute to risk of death through seizure, cardiac arrhythmia, hyperthermia or water intoxication.  MDMA may cause inappropriate release of the endogenous hormone ADH (antidiuretic hormone) that can cause low serum sodium, brain edema and death via water intoxication.

Given the acute toxic effects on multiple users of 2C-E in Oklahoma, the potential for toxic contaminants will need to be explored. 2C-E is thought to block the 5-HT2A (serotonin) receptor.  There is some evidence this effect is potentiated in those taking a selective serotonin reuptake inhibitory antidepressant drugs like Prozac.  Some of these designer drugs can be ordered online.  There is essentially no safety data so users are the defacto guinea pigs.  Autopsy results in the Oklahoma death will not be known for weeks.

Here is a listing of the compounds listed by parent compound type from a recent research review that explored the metabolism of these compounds.

2C phenethylamine compounds

(2C-B), 4-bromo-2,5-dimethoxy-beta-phenethylamine

(2C-I), 4-iodo-2,5-dimethoxy-beta-phenethylamine

(2C-D), 2,5-dimethoxy-4-methyl-beta-phenethylamine

(2C-E), 4-ethyl-2,5-dimethoxy-beta-phenethylamine

(2C-T-2), 4-ethylthio-2,5-dimethoxy-beta-phenethylamine and

(2C-T-7) 2,5-dimethoxy-4-propylthio-beta-phenethylamine

Beta-keto designer drugs

 (butylone, bk-MBDB), 2-methylamino-1-(3,4-methylenedioxyphenyl)butan

(ethylone, bk-MDEA), 1-one2-ethylamino-1-(3,4-methylenedioxyphenyl)propan

(methylone, bk-MDMA) 2-methylamino-1-(3,4-methylene notdioxy notphenyl)propan

pyrrolidino notphenones

(MPBP) 4-methyl-pyrrolidinobutyrophenone

(PVP) alpha-pyrrolidinovalerophenone

(PCPr) N (1 phenylcyclohexyl) propanamine

phencyclidine (PCP)-derived drugs

(PCEEA),N-(1-phenylcyclohexyl)-2-ethoxyethanamine

PCMPA), N-(1-phenylcyclohexyl)-3-methoxypropanamine

(PCMEA), (N-(1-phenylcyclohexyl)-2-methoxyethanamine

Tryptamines

(5-MeO-DIPT), 5-methoxy-N,N-diisopropyl nottryptamine

Alpha methylfentanyl

(alpha-MF) alpha-methylfentanyl

(3-MF) 3-methylfentanyl

Cannabis Compounts-K2, Spice

Cannabicyclohexanol

HU-210

JWH-018

JWH-073

Chemical model of the drug 2C-E from Wikipedia Creative Commons authored by sbrools.

Farah R, & Farah R (2008). Ecstasy (3,4-methylenedioxymethamphetamine)-induced inappropriate antidiuretic hormone secretion. Pediatric emergency care, 24 (9), 615-7 PMID: 18797371

Meyer MR, & Maurer HH (2010). Metabolism of designer drugs of abuse: an updated review. Current drug metabolism, 11 (5), 468-82 PMID: 20540700

Ecstasy Acute Effects on Social Cognition

MDMA (Ecstasy) Chemical Structure

Anecdotal reports suggest that some users of ecstasy (3,4-methlenedioxymethamphetamine-MDMA) experience increased feelings of empathy and are more social while under influence of the drug.  Such effects may contribute to the timing and frequency of ecstasy use and may also contribute to risk of abuse or dependence.  Understanding this phenomenon in more detail might provide clinicians with better strategies to reduce use and the associated complications of ecstasy use.

Studying acute effects of illicit drugs is difficult under natural conditions.  Users of ecstasy commonly also use alcohol, nictoine and other illicit drugs in the context of ecstasy use.  Isolating psychological effects of one agent in this type of environment is difficult if not impossible.  One alternative is to admiinster ecstasy in a laboratory setting with subjects blind to whether ecstasy or placebo is being administered.  However, this approach poses significant ethical challenges.  One approach, is to limit human study in the lab to those who have previously use ecstasy and intend to continue using.  Although imperfect, this approach limits risk of exposing ecstasy naive individuals to an illicit drug that may have reinforcing effects and increase risk of future drug use.

Chemical Structure of Methamphetamine

A study in Biological Psychiatry took this approach when over four sessions, healthy ecstasy using volunteers received either a low or high dose of MDMA, a dose of methamphetamine (METH) or placebo.  MDMA and methamphetamine share chemical (see chemical structures), pharmacological as well as psychological features.  Methamphetamine is typically considered a compound that increases CNS dopamine and norepinephrine while MDMA is felt to also increase CNS serotonin.   Ratings on a series of psychometric measures were obtained over a period of six hours after drug administration.  Visual analog scales (VAS) rated subjective feelings in a variety of domains: stimulated, bored, sedated, anxious, insightful, nauseated, loving, dizzy, sociable, confused, lonely, elated, playful, blank and restless.  Additionally, the rated themselves on the 72-item Profile of Mood States (POMS).  Subjects also completed a facial affect recognition task where they were asked to identify four facial emotions: anger, fear, happiness, sadness.

Here is a summary of the study findings for active agents compared to placebo:
MDMA (high dose) increased subjective VAS ratings of feeling "loving" and "friendly"
MDMA (low dose) increased subjective VAS ratings of "lonely"
MDMA (high dose) and METH increased VAS ratings of "playful"
METH alone increased VAS ratings of "sociability"
MDMA (high dose) reduced the accuracy of recognizing angry faces

So there is some support in this study for the anecdotal reports of increased prosocial cognition with MDMA.  The authors note their findings suggest MDMA increases social approach (sociability) rather thanThe authors note the study supports the possibility that increased social behavior with MDMA might be due to a reduced sensitivity to negative emotions of others rather than increasing recognition of positive emotions in others.  There also might be danger with this effect as social risk taking might increase potential for adverse consequences (connecting with someone you would be unlikely to connect with when not under the influence of MDMA).

Chemical structures of MDMA and methamphetamine from Wikipedia Creative Commons authored by Harbin.

Bedi G, Hyman D, & de Wit H (2010). Is ecstasy an "empathogen"? Effects of ±3,4-methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others. Biological psychiatry, 68 (12), 1134-40 PMID: 20947066