Unique substance warnings

• Two-piece gel encapsulation ("hard capsules"): Dissolves fully within 10-60 minutes.
• Blotters: Orally administering (swallowing) substances whose identity is uncertain is a potential way to eliminate most of the effects from dangerous mimics like 25x-NBx (25x-NBOMe like 25I-NBOMe, and 25x-NBOH like 25I-NBOH, etc). 25I-NBOMe is widely rumored to be orally inactive; however, oral efficacy has not been disproven and apparent overdoses have occurred via oral administration. 25I-NBOMe (and other NB's like 25x-NBOMe, 25x-NBOH) has much lower oral bioavailability than sublingual, buccal, and sublabial administration. 25I-NBOMe, to which several deaths have been attributed.^[1][2][3][4] may commonly be mistaken for LSD by sellers and users.^[5]

• Inhalants (other than Nitrous oxide, or poppers in moderation): "Four mechanisms for acute, direct VSA-related deaths are discussed, viz anoxia, vagal inhibition, respiratory depression and cardiac arrhythmia. Of these, cardiac arrhythmia due to 'sensitization' of the heart to adrenaline is probably the most common and is well documented in experimental conditions. Deaths from cardiac arrhythmia during or soon after VSA are unpredictable, unpreventable and resuscitation is rarely successful. Previous uneventful sessions of abuse provide no protection from this mode of death."^[6]
• MAOIs: Tyramine causes hypertensive crises after MAO inhibition aka the "cheese effect" or "cheese crisis". Using a MAO inhibitor (MAOI), the intake of approximately 10 to 25 mg of tyramine is required for a severe reaction compared to 6 to 10 mg for a mild reaction. Tyramine rich food should also be avoided by people prone to headache and migraine. Stilton (a blue cheese) contains up to 217 mg tyramine per 100 grams.^[7]
• Psilocybin mushrooms: x mg psilocybin is stored in each fully developed fruit body. So the number of species is more relevant than the quantity.

Neurotoxicity

• See the substances listed in: Neurotoxicity

Chemical forms

• DXM: It should be noted that DXM in freebase form (as found in Robocough RoboTablets) is around 27-37% more potent than its hydrobromide form due to a higher concentration of DXM by weight. One should take this into account when calculating their dose to avoid a potential overdose.

Dosage

Steep dose response curve

• 2C-B: "There is a steep dose response curve. Over the 12 to 24 milligram range, every 2 milligrams can make a profound increase or change of response. Initially, one should go lightly, and increase the dosage in subsequent trials by small increments."^[8]
• 2C-P: 2C-P is known to have a steep dose-response curve, as little as a few extra milligrams separating a manageable dose and an overdose. Also, 2C-P can have a very slow onset if ingested, and peak effects reportedly do not occur for 3 to 5 hours. "There was one report of an experience in which a single dosage of 16 mg was clearly an overdose, with the entire experiment labeled a physical disaster, not to be repeated. A consistent observation is that there may not be too much latitude in dosage between that which would be modest, or adequate, and that which would be excessive. The need for individual titration would be most important with this compound."^[9]

Slow onset

• 2C-P: Onset 1-3 hours. - https://www.erowid.org/library/books_online/pihkal/pihkal036.shtml

Long half-life

The anecdotal estimated elimination half-life is 19 hours.^[10]

Routes of administration

• Ketamine: Ketamine taken intravenously quicker than 1.5 minute can cause breathing depression for short time (up to a minute). - Ketamine: Dreams and Realities, p276
• Nitrous oxide: Inhaling directly from canisters can freeze the throat.
• Poppers: An overdose via oral ingestion alkyl nitrites can lead to methemoglobinemia, coma, and death.^{[11][12][13][14][15]} Accidental aspiration of amyl or butyl nitrites may cause lipoid pneumonia.^[16]

Substances that cannot be taken intravenously

• Hydroxyzine: Intravenous forms are not available because they pose a risk of causing hemolysis.^[17]

Genotype

• MDMA: There is a small percentage of people, who due to their race and family history, have a lower level of the liver enzyme P450 2D6. This can cause them to be more sensitive to MDMA, requiring lower doses and extra caution should be taken.^[18]
• Nitrous oxide: Nitrous oxide causes an acute increase in plasma homocysteine that is more pronounced in patients with the methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C gene variant.^[19]
• THC: CYP2C9 genotype affects THC sensitivity significantly: Subjects with the *3/*3 genotype had 3-fold higher THC levels in their blood than subjects with the *1/*1 genotype. Those subjects with one copy of each gene (*1/*3) had intermediate THC levels that were about 2-fold higher than subjects with *1/*1.^[20]