MDA - Topic

The MDMA Experience
Pure MDMA salt is a white crystalline solid. It looks white and tastes bitter. The compound is chemically stable. MDMA does not readily decompose in heat, air or light. The optimal adult dose of racemic MDMA is probably around 120-130mg [around 2mg/kg of body weight i.e. about 125mg] but optimal dose ranges from perhaps 75mg to as much as 250mg. Pills sold in clubs often contain less. There are gender differences in response; proportionately to body-weight, women are normally more sensitive than men to the sub-acute and longer-term effects of MDMA, so their optimal dosage may be lower. The preferentially metabolised (+)-enantiomer ("mirror image") of MDMA is more active, more stimulating, more dopaminergic, more subjectively rewarding, and more neurotoxic than the (-)-enantiomer. MDMA is usually taken orally as a tablet, a capsule, or a powder. MDMA is readily absorbed from the gastrointestinal tract into the bloodstream. More rarely, the drug is snorted, smoked or injected.

Onset of action is normally within twenty to sixty minutes or so after administration. When MDMA is administered by the oral route, "coming up" is naturally faster on an empty stomach. Taking MDMA causes both an increased neuronal reuptake inhibition of the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) and also, critically, its increased synaptic release. The MDMA molecule is small enough to be taken up via the membrane-bound serotonin transporter into the presynaptic serotonin axon terminals. Here MDMA acts to reverse the normal direction of the so-called serotonin reuptake pump. Inside the nerve cell, MDMA alters the configuration of the transporter protein so it binds to cytoplasmic serotonin, after which the transporter dumps serotonin outside the cell, reversing the normal inward-bound direction of the transporter channel i.e. MDMA increases the rate of transporter-mediated serotonin outflow. The consequent additional flood of serotonin in the user's synapses is soon followed by an increased release of dopamine especially in the reward centres of the striatum and nucleus accumbens. Release of oxytocin, the "cuddle hormone", surges too via stimulation of the serotonin 5-HT(1A) receptors.

First-time MDMA users occasionally feel confused or anxious before the dose-dependent dopamine-release kicks in. A transient hint of nausea is common when coming up. Most of the body's serotonin is found outside the brain, notably in neurons of the enteric nervous system, our "little brain" inside the smooth muscles of the gut. The user's peak experience or plateau phase after the exhilarating dopaminergic "rush" doesn't last much more than ninety minutes to two hours. MDMA's primary effects wear off after some 3-4 hours. MDMA is more fat-soluble than its structural parent, so its speed of onset is slightly faster and its duration of action shorter. With oral MDMA dosing, peak concentration in the plasma follows after around two hours. Therapists then sometimes add(ed) a final 50mg booster-dose. Heavy recreational users are not always so restrained either in dosage ["stacking"] or top-up schedule ["piggybacking"].

The clarity and unique psychological effects of MDMA can be impaired by ethyl alcohol. Thus MDMA is best taken while completely sober, though a modest drink later to ease any comedown may be useful.

MDMA has a complex nonlinear pharmacokinetics. Taking higher and/or more frequent doses of the drug disproportionately increases levels of plasma MDMA. Higher levels substantially increase oxidative stress and magnify the risk of toxicity. MDMA is metabolised via N-demethylation to the active metabolite MDA; MDA can itself induce a state of sensual euphoria, though in humans the conversion rate from MDMA in the body is low. At least four other metabolites have been identified. MDMA is broken down mainly in the liver, primarily by the polymorphic cytochrome P450 enzyme CYP2D6. However, other enzymes are involved in its degradation beside CYP2D6; some of them, like CYP2D6 itself, are saturated at relatively low MDMA concentrations. MDMA metabolism seems to run up against such a metabolic saturation-point somewhere between 120 and 150mg. When the high-affinity enzymes are saturated, a disproportionately large increase in blood- and brain MDMA-concentrations may occur if the user then takes more of the drug. A large but variable quantity of the parent compound is excreted unchanged, especially when the drug is taken at higher doses; but the opportunities for MDMA recycling by the cost-conscious are normally wasted.

MDMA is sometimes described as a cross between a psychostimulant and a mild hallucinogen. Since it's a methoxylated amphetamine, MDMA is indeed structurally related to mescaline. MDMA's methylenedioxy (O-CH2-O-) group is attached to positions 3 and 4 of the aromatic ring of the amphetamine molecule. But hallucinations on MDMA taken at therapeutic dosages are extremely rare; and psychostimulants, unlike MDMA, don't typically induce a profound sense of inner peace. Thus MDMA exhibits a different profile both from the prototypical "serotonergic" 2,5-dimethoxy-4-methylamphetime (DOM), with its psychedelic 5-HT2A-mediated mechanism of action, and also from the prototypical "dopaminergic" stimulant (+)-amphetamine.

MDMA is perhaps best characterised as belonging to a functionally unique class of "empathogen-entactogen". These words don't mean a great deal in the MDMA-naïve state. The term "empathogen" to describe MDMA and other closely related phenethylamine "empathy drugs" [MDA, MDEA, MBDB] was proposed by Ralph Metzner, Dean of the California Institute of Integral Studies, at a 1983 conference at the University of California at Santa Barbara. The term "entactogen" was coined in 1986 by Dr David Nichols, Professor of Medicinal Chemistry and Pharmacology at Purdue University and co-founder of the Heffter Research Institute, to refer to substances that generate a sense of "touching within" or "produce a feeling in one's innermost being". Both terms are quite apt, though neither will win any marketing awards. MDMA can promote an extraordinary clarity of introspective self-insight, together with a deep love of self and a no less emotionally intense empathetic love of others. MDMA also acts as a euphoriant. The euphoria is usually gentle and subtle; but sometimes profound.

Culture, set and setting inevitably shape the MDMA experience. Idiosyncratic responses to MDMA aren't rare. MDMA has even been described as a drug that "could be all things to all people" (Dr Shulgin). Even so, MDMA's primary effects on the user are surprisingly consistent, unlike the wilder psychedelics such as LSD, psilocybin, or DMT. MDMA may feel mystical, magical or sublime; but it doesn't feel weird. The drug's influence feels highly controllable. MDMA tends to enrich the user's sense of self-identity, not diminish it. MDMA "provides a centering experience, rather than an ego diffusing experience" (Dr. Philip Wolfson), though it may also cause a "softening of the ego-boundaries". Sometimes a degree of derealisation on MDMA may occur, but rarely depersonalisation in the ordinary sense of the term. On the contrary, users feel they can introspectively "touch inside" to their ideal authentic self with total emotional self-honesty.

As well as acting as a "gateway to the soul", MDMA "opens up the heart". Taking MDMA induces an amazing feeling of closeness and connectedness to one's fellow human beings. MDMA triggers intense emotional release beyond the bounds of everyday experience. The drug also enhances the felt intensity of the senses - most exquisitely perhaps the sense of touch. The body-image looks and feels wonderful. Other people look and feel wonderful too. Minutes after dropping a pill, a lifetime of Judaeo-Christian guilt, shame or disgust at the flesh melt away to oblivion.

When MDMA is taken outdoors, the natural world seems vibrant and awe-inspiring, perhaps even enchanted. The experience of colour is gorgeously intensified. On MDMA, Dr Shulgin reported how mountains he'd observed many times before appeared to be so beautiful that he could barely stand looking at them. MDMA is not normally classed as an entheogen. "Entheogen" is a term proposed in 1979 by the scholars R. Gordon Wasson, Carl A.P. Ruck, Jonathan Ott, Jeremy Bigwood and Danny Staples for agents "generating the god or the divine within", shorn of any speculative metaphysics. Yet MDMA is used by a variety of spiritual practitioners of widely diverse beliefs as a gateway to the divine. Some MDMA users undergo life-changing spiritual experiences. Nicholas Saunders, author of the book E for Ecstasy (1993), cites a Benedictine monk who finds MDMA "opens up a direct channel to God". MDMA may not be "Christ in (al)chemical form", but if it had been present in the Eucharist, then we would all still be devout Christians, possibly for ever. A minority of first-time MDMA users undergo what the inventor of the Shulgin scale christened a Plus Four...