Dissociative Symptoms

The most common medications causing dissociative symptoms are morphine analogues and -pam benzodiazepines: -lam benzodiazepines seem to be less likely to cause dissociative symptoms.

Morphine analogues and -pam but not -lam benzodiazepines share a xanthine-similar 2-oxo group.

The amnestic properties of xanthine-similar molecules are apparent in the history of anesthesia, with an early-1900s practice of adding scopolamine to morphine during childbirth to add dissociative amnesia to analgesia in a state that they termed "twilight sleep": PMID 20310688.

A xanthine-similar 2-oxo group is shared with amobarbital, the medication perhaps most reliably used to induce a dissociative state, as well as other barbiturates and glutethimide, an erstwhile barbiturate replacement therapy and insomnia drug discontinued due to abuse potential.

Although buspirone does not share GABA receptor effects with barbiturates: PMID 2836252, it does share the 2-oxo group, and seems to contribute to dissociative symptoms.

Xanthine-similarity may be a mechanism for the commonly recognized dissociative effects associated with oxybate/Zyrem, pregabalin, gabapentin, as well as Z-drugs. IMG

Some hallucinogens include both a xanthine-identifying 2-oxo group and a phenylethylamine group.

These are expected to have dual mechanisms of action: direct activation of the D2/D3 receptor (phenylethylamine) and product inhibition of guanse, resulting in additional dissociative/hallucinogenic effects.

Serotonin also shares both phenylethylamine and xanthine-identifying 2-oxo structures. When a compound is noted to be associated with psychosis and serotonin receptor activation, it may share one or both of these structures.

It may be that similar structures in melatonin (phenylethyl-amiDE, rather than phenylethyl-amiNE) contribute to physiologic derealization in the dreamstate.

Parapsychosis is a syndrome which combines both dissociations and psychotic elements and may guide treatment of dissociations in BPD, PTSD, and some cases of schizophrenic psychosis. IMG

Alcoholic blackout may be the most common and most reproducable dissociative effect. Alcohol intake is known to be correlated to increased hypoxanthine and xanthine production PMID XXXX. Dextromethorphan, a xanthine analogue, is described primarily as a dissociative. IMG