Long term dangers of chronic or frequent use

Chronic or frequent use can be problematic with almost all substances, psychoactive or not. Luckily, as stated above, entheogens have very low addictive potential and most entheogenic substances have very few physi- ological risks concerning frequent use. Even so, one can form habits leading to unhealthy usage patterns. Naturally, all of the risks of one-time use are increased with the frequency of usage.
Additionally, some of these substances - when taken frequently - can exert stress on the immune system, leading to colds and other common sicknesses. Taking substances can be taxing on the body by changing metabolism, heart rate, brain chemistry etc.. This alone can require a few days of recovery in order to retain one’s good health. Furthermore, some substances decrease appetite and increase the desire to move, which can lead to expending more energy than usual. Please remember to let your body and mind recover after your journeys by giving it enough nutrition, time, and rest.
Due to the increased release of Serotonin or activation of 5HT receptors caused by the effects of several entheogens, once the substances wear off, travelers may experience temporary depression/serotonin depletion, which generally returns to normal within a week. With chronic use (especially with MDMA), Serotonin down-regulation can become an issue, leading to longer lasting depressions. This condition is generally cured by abstaining from substances related to serotonin release and time. Depending on severity, it can last from a month to years.

High or repeated-dose MDMA regimens have been shown to produce long-term changes in indices of serotonergic and axonal functioning in animals. Increasing evidence supports the view that these changes are at least partially the result of damage due to serotonergic neurotoxicity. The magnitude of these serotonergic changes varies with dose, species, and route of administration. Rodent studies have shown that changes in the core temperature of animals can increase or decrease MDMA neurotoxicity. The sustained acute pharmacological effects of MDMA may exhaust neuronal energy sources and antioxidant defenses, leading to dam- age. Metabolites of MDMA are another possible source of oxidative stress. It is unclear if these effects can be fully extrapolated to humans.

A growing number of studies describe cognitive differences between ecstasy users and nonusers. These studies have serious limitations, but suggest that some ecstasy users experience serotonergic changes and cognitive alterations. A recent study (2011) however, failed to demonstrate marked residual cognitive effects in ecstasy users. The investigators suspect that previous findings to the contrary may have been due to poor study design and interpretation flaws. However, the possible risks of neurotoxicity must be considered when assessing the potential administration of MDMA to humans.
Another risk for frequent use is a noticeable decrease in short term memory abilities. This is true for the habitual use of cannabis and MDMA. Other substances so far have not been shown to cause any decrease in memory functions beyond their acute effects. Memory functions usually recover with time and abstinence, though it may take months