Drugs of Abuse

Extracellular purinergic signaling is a known phenomenon ATP review 16715052, implicated in pain 34730998, 21376829, 11137153: changes in affinity for non-aenosine nucleotide 11578839, mediated by purinergic receptors 11587549, 

The most popular psychotropic worldwide, caffeine blocks the adenosine receptor, decreasing perceived need for sleep temporarily: PMID 20164566. As a xanthine, is may also act as a PNP product-inhibitor, consistent with other stimulants. IMG

Nicotinic acid/niacin is combined with ATP to produce NAD, NADH, NADP, NADPH, recognized as critical intermediaries in biosynthetic processes and electron transport. Nicotine is structurally similar to nicotinic acid. If nicotine acts as a nicotinic acid analogue, we would expect increased sleepiness/ bedtime use documented PMID 21443301 (precursor inhibition results in increased ATP and secondarily increased adenosine).

There is an epilepsy subtype that can be treated by nicotine, likely due to adenosine increase 33284031.

Nicotinic acid is also hypoxanthine similar, resulting in mild PNP inhibition, similar to other stimulants caffeine and amphetamines below. Thermogenic effect of niacin is well known. Note that both nicotine and amphetamine-similar stimulants decrease appetite, likely by decreasing xanthine via PNP inhibition.

Note that schizophrenia-like hallucinations are attributable to xanthine and hypothetically, guanine as a phenylethylamine and putative D2/3 agonist. Nicotine as a mild stimulant would tend to decrease PNP activity, sparing the patient somewhat from elevations in xanthine/guanine in a manner that is consistent throughout the day, perhaps accounting for the unusually strong association between schizophrenia and nicotine use PMID 29864763, 9812108.

Pitolisant is a mild stimulant that uses an ester one position away to create a phenethylamine-similar result. Deemed first-in-class, there is value to the company in not citing this similarity: instead, identifying an unusual response.

Psilocybin has a hypoxanthine-similar structure and likely acts as a PNP inhibitor, increasing inosine (Io). Intoxication so reliably includes severe nausea that preparations for vomiting are routine. The strong sense of connectedness/empathy described with intoxication is consistent with elevations in Io, as are the predominant symptoms of nausea/vomiting. 

Cathinones include the carbonyl group that may be interpreted by the body as a 6-oxo group. The combination of PNP inhibition (stimulant) and inosine-similarity suggests Io excess. Consistent with our hypothesis of increased ADH with hypoxanthine analogues, hyponatremia is a common medical complication of overdose PMID 29302196. IMG

Alcohol dramatically increases hypoxanthine and xanthine production, likely by inducing PNP. This may may explain alcohol's temporarily beneficial effects in both tinnitus and parkinsonism, as well as it notoriously bad effect on gout. Conversion to excess xanthine is consistent with risk of blackout and with headache, perhaps the quintessential neuropathic pain. IMG

Common symptoms of paranoia and increased appetite, colloquially known as "the munchies" is consistent with xanthine-similarity. 

Artificial THC analogues.

I have noticed a clinical association between alcohol and THC avoidance and BPD symptoms, consistent with hypoxanthine/xanthine's prominent roles in dissociative symptoms and parapsychosis.  IMG

CBD seems to be sufficiently similar to reduce fentanyl binding and potentiate naloxone binding, suggesting benefit in cases of opiate overdose.

17384130, 31881765 action on XOR

PCP-incuded psychosis significantly changed purine interconversion XXXX including xanthine. IMG

Cocaine is a topical anesthetic XXXX.

PMID 19760630

PMID 28993732