54. Psychomotor stimulants and nootropic agents
Psychomotor stimulants
Psychomotor stimulants are drugs that have a marked effect on mental function and behaviour, producing excitement and euphoria, reduced sensation of fatigue and an increase in motor activity.
The important drugs here are:
- Amphetamines and related compounds
- Cocaine
- Methylxanthines
- Caffeine
- Theophylline
Many of these drugs are drugs of abuse and don’t have any clinical use.
Intoxication, withdrawal and treatment of intoxication and withdrawal of these compounds is described in topics 24 and 25.
Many drugs are included in this category:
- Amphetamines
- Dextroamphetamine
- Methamphetamine (“speed”)
- Phenmetrazine
- Methylphenidate (Ritalin®)
- Designer drugs
- MDMA (ecstasy)
- Mephedrone
- Cathinone (khat)
- MDPV (bath salts)
Amphetamines are illegal substances. People try to get around this illegality by producing designer drugs. These drugs are structurally or functionally similar to illegal drugs like amphetamines, but they’re not (yet) classified as illegal or detected on drug tests.
Mechanism of action
Amphetamines stimulate the release of the monoamines dopamine, norepinephrine and serotonin in the CNS.
They achieve this by acting as false substrates for norepinephrine transporter (NET)/uptake-1 and VMAT. This causes noradrenaline to leave the cytosol of the noradrenergic nerve ending and enter the synaptic cleft through NET.
These actions cause:
- Locomotor stimulation
- Stereotypical behaviour
- Euphoria
- Excitement
- Anorexia
- Increased heart rate
- Increased blood pressure
- Increased metabolism
Clinical indications:
- Narcolepsy (methylphenidate)
- Children with ADHD (methylphenidate)
Pharmacokinetics
Amphetamines are readily absorbed from the GI tract, and they cross the blood-brain barrier. The effects of amphetamines last for a few hours. They’re mainly excreted unchanged in the urine.
Cocaine
Cocaine and crack originate from the coca leaves. The effects of cocaine are similar to that of amphetamines, except it has less tendency to cause delusions and hallucinations.
Clinical indications
Cocaine’s only clinical use is as a local anaesthetic.
Mechanism of action
Cocaine competitively inhibits the uptake-1 mechanism, thereby preventing noradrenaline from being removed from the synaptic cleft. This increases monoamine transmission in the CNS and increasing peripheral sympathetic nerve activity. It also blocks sodium channels when applied locally and can therefore be used as a local anaesthetic.
These actions cause:
- Euphoria
- Locomotor stimulation
- Increased pleasure
- Reduced fatigue
- Increased heart rate
- Increased blood pressure
- Increased metabolism
Dosing
Cocaine is taken IV or through inhalation. Crack can be smoked.
Pharmacokinetics
Cocaine is rapidly metabolised by the liver, so its duration of action is much shorter than that of methamphetamine. Cocaine metabolites are deposited in hair, which can be detected during drug tests.
Methylxanthines
The most important methylxanthines are caffeine and theophylline.
Indications
Theophylline is used clinically as a bronchodilator. Caffeine is used as an adjunct to paracetamol to increase the painkiller effect, and to stimulate breathing in apnoeic neonates.
Mechanism of action
Methylxanthines are adenosine antagonists and phosphodiesterase inhibitors. By inhibiting phosphodiesterase (PDE) these drugs increase the intracellular level of cAMP. These mechanisms cause multiple effects:
- Psychomotor stimulation (without euphoria)
- Reduction of fatigue
- Improved concentration
- Diuresis (by vasodilation of the afferent arterioles in the kidney)
- Stimulation of cardiac muscle
- Bronchodilation
Dependence
Caffeine causes mild physical and psychological dependence. Withdrawal symptoms involve fatigue, headache and sleep disturbances.
Introduction to psychomimetic drugs
Psychomimetic drugs or hallucinogens are drugs that affect thought, perception and mood without causing psychomotor stimulation. They do no cause euphoria or psychological or physiological dependence.
We distinguish two groups:
- Those that are structurally similar to neurotransmitters
- LSD
- Psilocybin
- Mescaline
- Those that are structurally unrelated to neurotransmitters
- Cannabis
LSD
Lysergic acid diethylamide (LSD) is one of the most widely known and used hallucinogens. It’s a liquid but is often taken as small squares of paper that are soaked in it.
LSD is an agonist for 5-HT1A ,5-HT2A and 5-HT2C receptors in the CNS. This induces hallucinations. The thought processes become illogical and disconnected.
Intoxication
Sometimes a “bad trip” can occur, in which the person experiences paranoid delusions. Sometimes a person can experience “flashbacks” weeks later, where the person experiences visual hallucinations and delusions weeks after taking LSD.
Psilocybin
Psilocybin is the active ingredient in magic mushrooms. Its effects are similar to those of LSD, but last shorter and are less intense.
Mescaline
Mescaline is the active ingredient in the Peyote cactus. It induces a dream-like state.
Cannabis
The active hallucinogenic ingredient in cannabis is tetrahydrocannabinol (THC). THC binds to cannabinoid receptors in the CNS and causes hallucinogenic effect similar to but less pronounced than LSD.
Introduction to nootropic drugs
Nootropic drugs are drugs that aim to improve cognitive functions like memory, attention, concentration, etc. Unlike psychomotor stimulants these drugs don’t stimulate the CNS.
Some of these drugs can be useful in CNS disorders like stroke, Alzheimer, dementia and after brain trauma. Many of them have no proven cognitive effects and are taken by people with the belief that they can give “Limitless[1]” effects.
These drugs work by enhancing the cerebral microcirculation, by:
- Vasodilation
- Inhibiting platelet aggregation
- Reducing blood viscosity
- Improving metabolism in the brain
- Protecting against free radicals
- Modifying neurotransmitter systems in the brain
The important drugs here are memantine, piracetam, vinpocetine, pentoxifylline and gingko biloba extract.
Pentoxifylline was mentioned as a treatment for PAD in topic 8, but it is sometimes taken by people who believe it will increase their cognitive capacity. The same goes for vinpocetine and gingko biloba extract.
Indications
Memantine is used to improve moderate-to-severe Alzheimer disease.
Piracetam is used to treat myoclonus.
Mechanism of action
Memantine is a NMDA glutamate receptor antagonist that decreases glutamate-mediated excitotoxicity of the neurons.
Piracetam affects neurotransmitters in the CNS in a complex and poorly understood fashion.