Effects of the α₂-adrenergic agonist clonidine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine in healthy volunteers.
Study Goal
The researchers aimed to determine whether clonidine, an α₂-adrenergic receptor agonist, could mitigate the cardiovascular and psychotropic effects of MDMA by inhibiting norepinephrine release.
Results Summary
Clonidine reduced MDMA-induced increases in plasma norepinephrine and blood pressure but did not affect psychotropic effects or pharmacokinetics, indicating vesicular norepinephrine release is not critical to MDMA's effects in humans.
Population
16 healthy subjects
Effective Dosage
125 mg p.o. MDMA, 150 μg p.o. clonidine
Duration
Not specified
Interactions
Clonidine (no significant interaction with MDMA)
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
clonidine (150 μg p.o.) | decrease | MDMA-induced increases in plasma norepinephrine concentrations | 16 healthy subjects | - | reduced | #1 |
clonidine (150 μg p.o.) | decrease | MDMA-induced increases in blood pressure | 16 healthy subjects | - | reduced | #2 |
clonidine | decrease | norepinephrine levels | 16 healthy subjects | - | lowered | #3 |
clonidine | decrease | blood pressure | 16 healthy subjects | - | lowered | #4 |
clonidine | no change | psychotropic effects of MDMA | 16 healthy subjects | - | did not affect | #5 |
clonidine | no change | pharmacokinetics of MDMA | 16 healthy subjects | - | did not affect | #6 |
MDMA (125 mg p.o.) | increase | plasma norepinephrine concentrations | 16 healthy subjects | - | increases | #7 |
MDMA (125 mg p.o.) | increase | blood pressure | 16 healthy subjects | - | increases | #8 |
The mechanism of action of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) involves the carrier-mediated and potentially vesicular release of monoamines. We assessed the effects of the sympatholytic α₂-adrenergic receptor agonist clonidine (150 μg p.o.), which inhibits the neuronal vesicular release of norepinephrine, on the cardiovascular and psychotropic response to MDMA (125 mg p.o.) in 16 healthy subjects. The study used a randomized, double-blind, placebo-controlled crossover design with four experimental sessions. The administration of clonidine 1 h before MDMA reduced the MDMA-induced increases in plasma norepinephrine concentrations and blood pressure but only to the extent that clonidine lowered norepinephrine levels and blood pressure compared with placebo. Thus, no interaction was found between the cardiovascular effects of the two drugs. Clonidine did not affect the psychotropic effects or pharmacokinetics of MDMA. The lack of an interaction of the effects of clonidine and MDMA indicates that vesicular release of norepinephrine, which is inhibited by clonidine, does not critically contribute to the effects of MDMA in humans. Although clonidine may be used in the treatment of stimulant-induced hypertensive reactions, the present findings do not support a role for α₂-adrenergic receptor agonists in the prevention of psychostimulant dependence.