A euphoriant (or euphorigenic) is a type of psychoactive drug which tends to induce feelings of euphoria,12 the effects of which may include relaxation, anxiolysis, stress relief, mood lift, pleasure, and a rush although these effects are not necessary for a drug to be a euphoriant. Many euphoriants are notorious for their problems with abuse, addiction, and dependence. These agents are thought to induce their reinforcing effects by activating the so-called pleasure centers of the brain such as the ventral pallidum, nucleus accumbens, olfactory tubercle, and ventral tegmental area.
Stimulants are dopamine and sometimes norepinephrine reuptake inhibitors or releasing agents which include drugs such as amphetamine and methamphetamine (releasing agents) and cocaine and methylphenidate (reuptake inhibitors). Nicotine is a stimulant with a unique mechanism of action, affecting nicotinic acetylcholine receptors in the central nervous system. Tobacco, the plant from which nicotine is derived (and usually consumed whole, except in the case of nicotine replacement therapy) offers additional and synergistic stimulant effects when smoked, containing substances that inhibit the monoamine oxidases, primarily MAO-B, thus raising concentrations of all catecholamines in the brain.citation needed
Kappa-opioid receptor antagonists are also capable of inducing euphoria. Certain drugs, such as buprenorphine, are both mu-opiate agonists and kappa-opioid antagonists, thereby creating euphoria through multiple mechanisms at once.
The effects of hallucinogens can be euphoric in some people, in some situations, generally amplifying the emotions of the user.4 Unlike many other euphoriants, hallucinogenic drugs will usually increase the intensity of depression in a depressed person, or increase anxiety, even in those who do not have an anxiety disorder.4 Hallucinogens will, likewise, increase the intensity of mild happiness or euphoria exponentially.citation needed
The effects of hallucinogens are drastically different in different people, and even in the same person on two different occasions,4 especially with a different mind-set or in different situations. Having a good mindset and physical setting are absolutely necessary to have a good experience using a hallucinogen. Mentally ill people, especially people with schizophrenia or anxiety disorders, usually have a negative reaction to hallucinogens.4 People with a family history of mental illness have a higher than normal chance of adverse reaction.4
Deliriants are a class of drugs which is primarily represented by anticholinergic drugs, of which first-generation antihistamines are prototypical.5 Others include orphenadrine, scopolamine, and atropine. Their euphoric effects are fairly mild and unpredictable in different people, some being more susceptible than others, therefore overall having a low potential for abuse.citation needed
Many euphoriants have a "mixed" mechanism of action (MOA), which is to say they don't categorize neatly in to one of the above groups, or affect more than one system of receptors or neurotransmitters. Some drugs have a predominant mechanism of action at certain doses, and another mechanism of action becomes predominant at higher doses. Some drugs have a mixed mechanism of action at all doses, and some drugs have vastly different mechanisms of action depending on the stereoisomer used.citation needed
- Cocaine has a tendency to induce psychosis and seizures in high doses, likely linked to its agonism of the sigma receptor, which is minor with moderate dosage.
- Tramadol, a weak mu-opioid agonist, serotonin releasing agent, norepinephrine reuptake inhibitor, and NMDA-antagonist
- Methadone, being a potent mu-opioid agonist in lævo-rotatory form and NMDA-antagonist in dextro-rotatory form. The only commercially available preparations are the racemate, so the drug has, in effect, a mixed mechanism of action, even though one specific stereoisomer of the drug is responsible for each unique pharmacological action. Its effects are mostly that of an opioid, with some dissociative effects from NMDA-antagonism based on the dosage.citation needed
- Pentazocine is a mixed-opioid receptor agonist, and sigma receptor agonist. In low doses, it causes effects similar to that of low-dose morphine - in higher doses, dissociation, hallucinations, and delirium are common, as the effects upon kappa opioid receptors and the sigma receptor become more prominent.citation needed
- Dimethyltryptamine (DMT), a naturally-occurring hallucinogen produced by many plants and found in trace amounts in the mammalian brain, has effects on both the serotonin receptors and the sigma receptor, causing a combination of psychedelic and dissociative effects.citation needed