Dissociative Drugs, Hallucinogens, Caffeine, Inhalants, and Other Substances of Abuse

Ketamine

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  Ketamine is a noncompetitive antagonist of the NMDA receptor. At the NMDA receptor, ketamine prevents the influx of calcium and sodium ions. Currently, it is used as an anesthetic and for the treatment of pain and depression. Ketamine is also being investigated for the treatment of PTSD and cocaine use disorder.

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  Ketamine is a derivative of PCP; laboratory investigation of PCP led to the discovery of ketamine.

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  Ketamine exists in two enantiomers: S-ketamine and R-ketamine. Esketamine, which is U.S. Food and Drug Administration (FDA)-approved for depression and available as an intranasal spray, is made up of only the S-enantiomer, which has more potent NMDA antagonism than the R-enantiomer. Intravenous ketamine is a racemic mixture of both enantiomers.

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  At higher doses, individuals consuming ketamine enter what is popularly known as the “K-Hole”—a dissociative state commonly described as an out-of-body experience.

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  The acute effects of ketamine intoxication include amnesia, dilated pupils, nystagmus (although less than PCP), and increased heart rate and blood pressure.

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  Ketamine can be found in different compounds like in a white powder, liquid, and pill form.

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  Ketamine overdose can lead to respiratory depression, apnea, and death, although the lethal dose is about 50 times higher than the typical recreational dose.

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  It is used as a dissociative anesthetic and for the treatment of pain and depression.

PCP

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  It is an NMDA antagonist and a dopamine type 2 receptor partial agonism.

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  PCP-induced psychosis resembles schizophrenia in both positive and negative symptoms. In fact, PCP animal models are used to study medications for schizophrenia.

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  The effects of PCP include dissociation, hallucinations, paranoia, analgesia, and violence. Other signs and symptoms of PCP intoxication include hypertension, nystagmus, and ataxia. An overdose with PCP can lead to coma, seizures, and death.

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  Repeated PCP administration can cause a disruption in glutamate transmission and γ-aminobutyric acid function in the prefrontal cortex, causing symptoms similar to schizophrenia.

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  PCP was used as an intravenous human and veterinary anesthetic, but it was replaced by ketamine due to its adverse effect of prolonged delirium.

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  PCP’s false-positive urine screens can occur with tramadol, dextromethorphan, alprazolam, clonazepam, carvedilol, and diphenhydramine.

DXM

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  It is an over-the-counter cough suppressant. It is frequently sold in combination with other medications like chlorpheniramine or acetaminophen. Cough syrups with DXM are widely abused for their dissociative and euphoric effects (a.k.a. “robotripping”), mainly by teenagers and young adults.

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  In addition to being an NMDA antagonist, DXM is also a sigma-1-opioid receptor agonist and a nonselective serotonin reuptake inhibitor.

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  DXM is a synthetic analog of levorphanol, which is an opioid that is structurally similar to morphine.

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  At low doses, DXM has opioid-like effects (which account for its efficacy as a cough suppressant); at higher doses, it acts as a dissociative and hallucinogen.

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  DXM intoxication signs and symptoms include dilated pupils, tachycardia, hallucinations, psychosis, serotonin syndrome, seizure, and rhabdomyolysis.

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  Bromism, or abnormally elevated bromide levels from hydrobromide ions in cough syrups, can occur in DXM intoxication. Symptoms include fatigue, headache, and memory loss. Bromism will cause an anion gap and elevated chloride levels.

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  In DXM overdose, can give charcoal and, at high doses, naloxone. Because DXM products frequently contain acetaminophen, one must also evaluate for acetaminophen overdose and hepatotoxicity. No specific antidote exists for DXM toxicity.

Tryptamine Hallucinogens

Tryptamine is a chemical structure that is shared by LSD, psilocybin, DMT, and the neurotransmitter serotonin.

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  Ayahuasca ( Banisteriopsis caapi ) is a plant that naturally contains both N,N-dimethyltryptamine (DMT) and monoamine oxidase inhibitors (MAOIs). Due to naturally occurring MAOIs, ayahuasca carries a higher risk of serotonin syndrome when combined with other serotonergic agents. The plant is used as a traditional spiritual medicine in ceremonies among the indigenous people of the Amazon

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  Psilocybin is a natural hallucinogen produced by certain species of mushrooms. Once ingested, it is metabolized to psilocin which has potent serotonergic and hallucinogenic effects.

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  LSD is a synthetic hallucinogen. It acts on multiple serotonin receptors, including 5-HT2A, and has D2 receptor agonism that sets it apart from other hallucinogens.

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  Morning glory: Seeds from some of its species have hallucinogenic effects. The seeds contain lysergic acid amide, a chemical like LSD.