Recreational Drugs Which Also Act At 5-HT2B Receptors
Several serotonergic recreational drugs, including the empathogens MDA and MDMA ("Ecstasy"), the piperazine derivative mCPP and some hallucinogens such as DOI and bromo-dragonfly, have all been shown to act as 5-HT2B agonists in vitro, but how significant this may be as a risk factor associated with their recreational use is unclear. One study of human users of "ecstasy" found that they did have heart valve changes suggestive of early cardiac fibrosis, which were not present in non-ecstasy using controls, suggesting that ecstasy use certainly has the potential to cause this kind of heart damage. On the other hand there is no statistical evidence as yet to suggest significant increases in rates of cardiac valvopathies in current or former MDMA users, and it is most likely that as with other 5-HT2B agonists, development of heart valve damage will be highly dependent on the frequency and duration of use and the total cumulative exposure over time, and only a small proportion of the heaviest users are likely to face a substantial risk of heart damage.
The chemist Alexander Shulgin first popularized MDMA and MDA, and he invented DOI and many other recreational drugs that are also 5HT-2B receptor agonists. In 2008 Shulgin underwent surgery to replace a defective aortic heart valve. It is unknown whether or not Shulgin's lifelong use of psychedelic drugs caused the failure of his heart valve.
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