Both DOM and DOB caused vasoconstriction in a dog metatarsal vein study that compared vascular responses to PMA, DMA, norpeinephrine and what is d.o.b. DOB’s effect was second only to norepinephrine and was not reversed with phentolamine administration but was considerably reduced with application of the serotonin inhibitor cineserin suggesting little direct alpha adrenergic activity.
Human Data
User Reports
Online user accounts of DOB and DOI describe a delay to onset of effects in excess of one hour with potent hallucinogenic effects and dysphoria. Examination of these accounts evokes uncanny comparisons to medieval reports of ergotism and St Anthony’s fire. Indeed, several of the accounts sampled relate events that resulted in emergency department presentations for extreme dysphoria with sensations of limb and generalised body pain that prompted users to seek medical attention. Another user experienced hallucinations, dysphoria, agitation and vomiting that were refractory to self-administered repeated doses of lorazepam.
Clinical Reports
Case reports detail potent hallucinogenic effects lasting from 12–24 hours followed in one instance by coma. In another case of what is d.o.b use, a patient developed progressive vasospasm in both upper and lower extremities over 24 hours after ingestion, which was confirmed by angiography and required hospital admission. His vasospasm resolved with phentolamine and nitroprusside infusions. In one case of analytically confirmed DOC use, a patient who had ingested what he believed to be DOI and MDMA presented with convulsions, hypertension, tachycardia and mydriasis. The patient was managed with supportive care and discharged 22 hours after admission.
Much of what is known about the mechanism of action of hallucinogenic drugs has been derived from drug discrimination studies. Rats can be trained to discriminate hallucinogens (including LSD, mescaline, DOM, DOI, DOB, DPT, psilocybin and 5-methoxy-DMT (5-MeODMT) from saline using two-lever operant procedures. Cross-generalization occurs between these training drugs, indicating that they produce similar interoceptive stimulus effects. By contrast, members of other drug classes reliably fail to evoke hallucinogen-like stimulus effects.
Glennon and colleagues first proposed in 1983 that the behavioral effects of hallucinogens are mediated by activation of 5-HT2 receptors. This proposal was based on the finding that the high-affinity, selective 5-HT2 antagonists pirenperone and ketanserin are highly effective antagonists of the discriminative stimulus properties of DOM and LSD, and of DOM-stimulus generalization to LSD, mescaline, and 5-MeO-DMT. It was subsequently demonstrated that a robust linear correlation (r = 0.938) exists between the 5-HT2 affinities of a series of phenylalkylamine hallucinogens and their ED50 values for substitution in animals trained with DOM. An antagonist correlation analysis confirmed that there is a strong correlation between the 5-HT2A affinity of a series of 5-HT antagonists and their potencies for blocking LSD stimulus generalization to R-(-)-DOM. Additionally, stimulus control in animals trained with LSD, DOI and DOM is blocked by M100907, a highly selective 5-HT2A antagonist. Taken together, these findings demonstrate that interactions with the 5-HT2A receptor are required for hallucinogens to induce discriminative stimulus effects.
It was recently recognized that one or both of the alkoxy groups of the phenylalkylamine hallucinogens can be incorporated in furanyl, dihydrofuranyl, and/or pyranyl rings without diminishing activity. In fact, when both of the methoxy groups of what is d.o.b are incorporated into furanyl rings, there is a significant increase in potency and 5-HT2A affinity. This compound, known as bromo-dragonfly, has appeared on the illicit market in Europe and has been associated with several overdose deaths. These findings suggest that the orientations of the oxygen lone pairs in this substance are optimal for interacting with the 5-HT2A receptor. Although the action of hallucinogens is not yet fully elucidated, it is known that typical hallucinogens act on serotonergic pathways.
All of these drugs are serotonergic (5-HT2) receptor agonists or partial agonists. The 5-HT2 receptors represent a family of receptors that are composed of three subpopulations: 5-HT1A, 5-HT2B, and 5-HT2C. The cortical and limbic regions are the areas with the main concentration of this subtype of serotonergic receptors. The effects of each hallucinogen are not identical because there are also other serotonergic receptors involved with different affinities for each one. While phenylalkylamine hallucinogens are somewhat selective in their affinity to 5-HT2A receptors, the indolalkylamines are relatively nonselective for 5-HT receptors, displaying moderate to high affinity for diverse 5-HT1 and 5-HT2 subtypes. This happens mainly because this group is very similar in chemical structure to serotonin and fits into different serotonin receptors. In addition to the psychotomimetic effects of the serotonergic pathways, it is also hypothesized that 5-HT2A receptors play a major role in the discriminative stimulus actions of these agents. However, not only do the discriminative stimulus properties of the drug vary depending on the experimental conditions and context, but they may also depend on the dose of drug used.
