Many psychoactive and psychedelic substances were used therapeutically in the mid-20th century, but became restricted or banned due to problems around their recreational use. Over the past decade, the potential for widely prohibited psychoactive or psychedelic drugs to be rescheduled as medicines has increased research activity in this area.¹

Psilocybin and ecstasy have been authorised for therapeutic use in Australia, while an LSD salt is gearing up for phase three trials in the USA. Researchers are also looking at expanding indications for psychoactive licensed medicines such as ketamine as studies build evidence for new specific purposes.^2,3,4

Areas of use include anxiety, stress, depression, and pain including migraine. Studies are increasingly supporting the view that psychedelics have a significant potential for treating neuropsychiatric diseases where conventional treatment is failing.^1,4,5,6

This article looks at developments supporting therapeutic applications of psychoactive drugs.

Midomafetamine – background

Midomafetamine, also known as 3,4-methylenedioxymethamphetamine, MDMA or ecstasy, was used in psychotherapy in the 1970s and 1980s. Anecdotally, psychiatrists found it helped patients open up about trauma in their lives.⁷

However, as a popular recreational drug, especially among clubbers, adverse effects became apparent. These include dancers’ body temperature increasing and overheating, while drinking too much water to cool down causes its own problems through electrolyte imbalance. The drug also causes urinary retention and increases blood pressure.^8,9

Studies on rodents showed MDMA also depleted serotonin neurons. This led to authorities around the world rescheduling MDMA as a Schedule 1 Controlled Drug.^7,8

While structurally similar to methylenedioxyamphetamine (MDA), a known hallucinogen, MDMA has an N-methylation and has different properties. One difference between MDA and MDMA is in the stereochemistry as the more active isomers of MDMA and MDA are opposites. In addition, MDMA’s pharmacology puts it in a separate class to hallucinogenic amphetamines like MDA.⁷

Rather than being classed as a hallucinogenic amphetamine like MDA, MDMA is considered an entactogen, with much less psychostimulant or hallucinogenic effects but being capable of more strongly promoting social bonding behaviour, reducing anxiety and increasing self-awareness leading to introspection and personal reflection.^7,10

Its activity derives from being transported by neuronal serotonin reuptake carriers and promoting release of serotonin (5-hydroxytryptamine or 5-HT) stored in neurones. Social affiliation due to MDMA appears to be due to serotonin release and 5-HT_1B receptor stimulation in the nucleus accumbens. This is the ‘pleasure centre’ of the brain associated with positive effect and feelings of reward, including those linked to motivation, behaviour and addiction.^7,11