Dissociative drug

A dissociative is a drug which reduces (or blocks) signals to the conscious mind from other parts of the brain, typically, but not necessarily, limited to the senses. Such a state of sensory deprivation and dissociation can facilitate self-exploration, hallucinations, and dreamlike states of mind which may resemble some psychedelic mindstates. Essentially, similar states of mind can be reached via contrasting paths—psychedelic or dissociative. That said, the entire experience's risks and benefits are markedly different.

The primary dissociatives are similar in action to phencyclidine (PCP), and include ketamine and dextromethorphan (DXM). Also included are nitrous oxide (laughing gas), salvia divinorum, and muscimol from the amanita muscaria (fly agaric) mushroom.

Many dissociatives also have central nervous system depressant effects, thereby carrying similar risks with opioids that slow breathing and lower the heart rate to levels which can result in death, when used in very high doses.

Their effects are characterized by intense feelings of depersonalization, derealization, and analgesia.

Pharmacological classes of dissociatives, and their general subjective effects

Entries marked with a "#" are naturally occurring.

NMDA Receptor Antagonists

Uncompetitive channel blockers include:
* Amantadine [ [http://www.clinicaltrials.gov/ct/show/NCT00188383?order=4 "Effects of N-Methyl-D-Aspartate (NMDA)-Receptor Antagonism on Hyperalgesia, Opioid Use, and Pain After Radical Prostatectomy"] , University Health Network, Toronto, September 2005]
* AP5 (2-amino-5-phosphonopentanoate), a competitive glutamate antagonist selective for the NMDA-R.
* Dextromethorphan
* Dextrorphan
* Ibogaine # [Popik P, Layer RT, Skolnick P (1994): "The putative anti-addictive drug ibogaine is a competitive inhibitor of [3H] MK-801 binding to the NMDA receptor complex." Psychopharmacology (Berl), 114(4), 672-4. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=7531855&query_hl=20&itool=pubmed_docsum Abstract] ]
* Phencyclidine
* Ketamine
* Tiletamine
* Rolicyclidine
* Eticyclidine
* Tenocyclidine
* Dizocilpine
* Nitrous oxide #
* Xenon #
* Riluzole

Most members of the noncompetitive channel-blocker group are arylcyclohexylamines. Their molecular structure includes a cyclohexyl ring, a piperidine ring and a phenyl group. [ AJ Giannini. Drugs of Abuse--Second Edition. Los Angeles, Practice Management Information Corp, 1997.] The gases nitrous oxide and xenon are obvious exceptionsNon-competitive antagonists include:
*Aptiganel (Cerestat, CNS-1102). Binds the Mg²⁺ binding site within the channel of the NMDAR.
*Memantine (Axura, Akatinol, Namenda, Ebixa, 1-amino-3,5-dimethylada-mantane). Approved in the U.S. by the Food and Drug Administration for the treatment of Alzheimer's disease.cite journal | last =Chawla | first = PS| authorlink = | coauthors = Kochar MS| title =What's new in clinical pharmacology and therapeutics | journal =WMJ | volume =105 | issue = 3| pages =24–29 | publisher = | date =2006 | url =http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16749321&query_hl=23&itool=pubmed_docsum | doi = | pmid =16749321 | accessdate =2007-01-17 ]
*Remacimide. Principle metabolite is an uncompetitive antagonist with a low affinity for the binding site.cite journal | last = Muir | first =KW | authorlink = | coauthors = | title =Glutamate-based therapeutic approaches: clinical trials with NMDA antagonists | journal =Current Opinion in Pharmacology | volume =6 | issue =1 | pages = 53–60| publisher = | date =2005 | url = | doi = 10.1016/j.coph.2005.12.002| pmid =16359918 | accessdate =2007-01-17 ]

Drugs that act at the glycine binding site include 7-chlorokynurenate.

κ-opioid receptor agonists

*Salvinorin-A #, the active constituent of "Salvia divinorum" (diviner's sage)
*Enadoline
*ibogaine (Weak / Complex mechanism of action)
*Pentazocine

σ-opioid receptor agonists

*Noscapine, a minor alkaloid found in opium

Amanita muscaria constituents

*Muscimol # GABA-A agonist, primary active constituent
*Ibotenic acid # NMDA agonist, neurotoxin, metabolizes to muscimol or can be converted into muscimol by heating at 170 C
*Muscarine # muscarinic ACh agonist, trace constituent, not active in brain but causes physical side effects

These four groups of dissociatives have slightly different effects but also share similarities separating them from other classes of hallucinogens. They are markedly different from psychedelics such as LSD, where alert and fully conscious users experience cognitive distortion while simultaneously interacting with the "real world". Hallucinations from these dissociatives are generally only experienced in dark rooms or with eyes closed, unless at very high doses above what is normally consumed recreationally. Nitrous oxide has very different effects however, and even at low doses includes auditory distortions. Unlike with many other psychedelic chemicals, salvia users are generally not ambulatory and the experience is frequently dissociative. Often a very brief trance is entered, where the user experiences an intense and very realistic dream state. On the other hand, the effect of salvia on emotion has been reported to be less marked than that of true psychedelics.

Although muscimol does not usually cause normal hallucinations, it has a tendency to put the user to sleep, during which the user is able to have very vivid dreams with good dream recall.

See also

*Deliriant
*Psychedelic drug
*Psychedelics, dissociatives and deliriants
*Psychoactive drug

References