Hallucinogens

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Chapter: Essential pharmacology : Drugs Used In Mental Illness: Antipsychotic And Antimanic Drugs

These are drugs which alter mood, behaviour, thought and perception in a manner similar to that seen in psychosis. Many natural products having hallucinogenic property have been discovered and used by man since prehistoric times.


HALLUCINOGENS

(Psychotomimetics, Psychedelics, Psychodysleptics, Psychotogens)

 

These are drugs which alter mood, behaviour, thought and perception in a manner similar to that seen in psychosis. Many natural products having hallucinogenic property have been discovered and used by man since prehistoric times. A number of synthetic compounds have also been produced. The important ones are briefly described below.

 

Indole Amines

 

Lysergic Acid Diethylamide (LSD)

 

Synthesized by Hofmann (1938) who was working on chemistry of ergot alkaloids, and himself experienced its hallucinogenic effect. It is the most potent psychedelic, 25–50 μg produces all the effects. In addition to the mental effects, it produces pronounced central sympathetic stimulation. Its action appears to involve serotonergic neuronal systems in brain.

 

Lysergic Acid Amide 

 

A close relative of LSD but 10 times less potent; found in morning glory (Ipomoea violace) seeds.

 

Psilocybin

 

Found in a Mexican mushroom Psilocybe mexicana; it has been used by Red Indian tribals during religious rituals.

 

Harmine

 

It is present in a vine Banisteriopsis caapi, found in the Amazon region. The Brazilian natives have used it as a snuff.

 

Bufotenin

 

Isolated from skin of a toad (Bufo marinus). It is also found in ‘Cohaba Snuff’ and in the mushroom Amanita muscaria.

 

The above are all Indolealkylamines related chemically to 5HT. A number of other synthetic derivatives like Dimethyltryptamine (DMT) are also hallucinogenic.

 

Phenylalkylamines

 

Mescaline

 

From Mexican ‘Peyote cactus’ Lophophora williamsi. It is a low potency hallucinogen used by natives during rituals. It is a phenylalkylamine but does not have marked sympathomimetic effects.

 

Ecstasy

 

Methylene dioxy methamphetamine (MDMA) is an amphetamine-like synthetic compound with stimulant and hallucinogenic properties, that has been abused as a recreational and euphoriant drug, especially by college students under the name ‘Ecstasy’. Fear of neurotoxicity has reduced its popularity.

 

Other synthetic phenylalkylamines with hallucinogenic property are—Dimethoxymethyl amphetamine (DOM) and Methylene dioxyamphetamine (MDA). High doses and repeated use of amphetamine can also cause psychosis.

 

Arylcyclohexyl Amines

 

Phencyclidine

 

It is an anticholinergic, which activates receptors in brain causing disorientation, distortion of body image, hallucinations and an anaesthetic like state: ketamine is a closely related compound with lower hallucinogenic potential and is used in anaesthesia.

 

Cannabinoids

 

Tetrahydrocannabinol (9 THC)

 

It is the active principle of Cannabis indica (Marijuana). It has been the most popular recreational and ritualistic intoxicant used for millennia. Its use has spread world wide. The following are the various forms in which it is used.

 

Bhang the dried leaves—is generally taken by oral route, acts slowly.

 

Ganja the dried female inflorescence—is more potent and is smoked: effects are produced almost instantaneously.

 

Charas is the dried resinous extract from the flowering tops and leaves—most potent, smoked with tobacco; also called ‘hashish’.

 

Cannabis is the drug of abuse having lowest acute toxicity.

 

Considerable insight has been obtained recently in cannabinoid pharmacology. Since 1990 two cannabinoid receptors CB1 (in CNS) and CB2 (in peripheral tissues) have been identified and cloned. A host of endogenous ligands for the cannabinoid receptors have also been isolated. Anandamide the ethanolamide of arachidonic acid is the principal endocannabinoid synthesized in the brain. Endocannabinoids are released by macrophages during haemorrhagic shock and cause fall in BP. However, all actions of cannabis are not mimicked by anandamide.

 

Cannabis produces potent analgesic, antiemetic, anti-inflammatory and many other pharmacological actions. The crude herb, its active constituents and some synthetic analogues have been tried in a variety of conditions and many potential clinical applications are proposed.

 

ü To ameliorate muscle spasm and pain in multiple sclerosis, and certain dystonias.

ü Cancer chemotherapy induced vomiting: the synthetic cannabinoids nabilone and dronabinol are licenced for this use.

ü As a neuronal protective after head injury and cerebral ischaemia.

ü To relieve anxiety; migraine.

ü To reduce i.o.t. in glaucoma.

ü As  appetite  stimulant.

ü As bronchodilator in asthma.

 

However, the hallucinogenic and psychomotor effects are a limitation; non-hallucinogenic congeners are being investigated.

 

The hallucinogens, in general, produce a dreamlike state with disorientation, loss of contact with reality, field of vision may appear to sway and objects distorted like images in a curved mirror, faces may appear grotesque. On closing the eyes an unending series of colourful, very realistic and fantastic images appear to surge; time sense is altered, music appears tangible. Ability to concentrate is impaired, one can read but does not know what he is reading; however, ataxia is not prominent. Many feel relaxed and supremely happy, may laugh uncontrollably or may become sad and weep. With higher doses—panic reactions and sinking sensation are common.

 

Some degree of tolerance occurs, but reverse tolerance is not unusual.

 

Psychological dependence on hallucinogens may be mild (occasional trips) to marked (compulsive abuse), but physical dependence does not occur. All are drugs of abuse.

 

Hallucinogens have been rarely used in psychiatry to facilitate conversation and for opening up the inner self in case of withdrawn patients.


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