Synthetic drugs – Entactogens –

“Entactogenic” means “facilitating contact”, a term originally coined in 1986 by David E. Nichols and Alexander Shulgin as an alternative to “empathogenic”, which they criticised for its possible association with the root pathos.

They are therefore products that produce a powerful contact with one’s inner self.

3,4-methylene dioxy-N-methaphetamine

MDMA is a synthetic substance commonly known as ecstasy , Adam, XTC, M&M and MDM, although the term is now generally used to designate a wide range of other substances. Originally developed in 1912 by the pharmaceutical company Merck, it was never marketed as a medicine. Although it has been offered as an aid in psychiatric consultations, its therapeutic use is extremely limited. The illicit form of MDMA is often in tablet form, much of which is manufactured in Europe. MDMA has a stimulant effect on the central nervous system (CNS) and a mild hallucinogenic effect, described more accurately as a stimulation of sensory awareness. MDMA is internationally controlled.

Forms and uses

The most common salt is the hydrochloride (CAS-64057-70-1), which is a white or off-white powder or water-soluble crystals. Phosphate salt is also found. Illegal products are mainly in the form of tablets with a distinctive logo and, less commonly, in the form of white powder or capsules. MDMA base is a colourless, water-insoluble oil.

MDMA (tablets) is almost systematically taken orally (swallowed), but in powder form it can be snorted, inhaled or injected, although injection is very rarely observed in recreational settings.

Synthesis

Four main precursors can be used to manufacture MDMA and related drugs: safrole, isosafrole, piperonal and 3,4-methylenedioxyphenyl-2-propanone (PMK).

Toxicokinetics

After ingestion, a very large proportion of MDMA is excreted unchanged in the urine.

The main metabolites are 3,4-methylenedioxyamphetamine (MDA) and O-demethylated compounds. After a dose of 75 mg, a maximum plasma concentration of about 0.13 mg/L is reached within 2 hours. The plasma half-life is 6-7 hours. In animals, MDMA induces neurotoxicity manifested by anatomical changes in axons and a sustained reduction in brain serotonin levels. The significance of these observations for human users is not yet clear, but it is known that MDMA use is associated with cognitive impairment. Some of the pharmacodynamic and toxic effects of MDMA vary depending on the enantiomer used. However, almost all illicit MDMA is in the form of a racemic mixture. Deaths have been reported after ingestion of a 300 mg dose, but toxicity depends on many factors, including individual susceptibility and the circumstances in which MDMA is used.

Effects

• In moderate amounts: increases pleasure, ease of contact, empathy
• In high doses: cardiac arrhythmias, hyperthermia, rhabdomyolysis, toxic coagulopathy, which can lead to death.
• Chronic use: irreversible damage to serotonergic neurons has been shown in animals, with a decrease in the level of 5-hydroxyindoleacetic acid (5HIAA) (a metabolite of 5HT) in the cerebrospinal fluid.
• This may explain chronic mood, sleep and impulse control disorders in chronic users.

Dependence

MDMA use is highly physically and psychologically addictive. Over 92% of MDMA users also take other even harder drugs, such as heroin and cocaine, because they feel an irresistible need to mix sensations by taking several substances at the same time.