Benzodiazepines

Fatal overdose may occur when benzodiazepines are combined with other depressants such as opiates, barbiturates, gabapentinoids, thienodiazepines, alcohol or other GABAergic substances.

It is strongly discouraged to combine these substances, particularly in common to heavy doses.

The core structure of benzodiazepines

Xanax (alprazolam) 2 mg tri-score tablets

Benzodiazepines (also referred to as benzos) are psychoactive drugs that act as central nervous system depressants. These drugs work by magnifying the efficiency and effects of the neurotransmitter gamma aminobutyric acid (GABA) by acting on its receptors. The prominent effects of benzodiazepines include anxiety suppression, sedation, muscle relaxation, disinhibition, and amnesia. Short-acting benzodiazepines are recommended for treating insomnia while long-acting ones are recommended for the treatment of anxiety disorders.

It's worth noting that withdrawal from extended benzodiazepine use can result in hypertension, seizures, and death. When suspending long-term use, it is highly recommended to taper one's dose by gradually lowering the amount taken each day for a prolonged period of time instead of stopping abruptly.

Chemistry

This chemistry section is incomplete. You can help by adding to it.

Benzodiazepine is a heterocyclic compound comprised of a benzene ring fused to a diazepine ring. Benzodiazepine drugs are substituted 1,4-benzodiazepines with different side groups attached to the central structure.

Pharmacology

Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site and magnifying the efficiency and effects of the neurotransmitter gamma aminobutyric acid (GABA) by acting on its receptors. As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the sedating (or calming effects) of benzodiazepines on the nervous system.

The anticonvulsant properties of benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects will rarely (if ever) occur all at once, but heavier dosages will increase the chances and are more likely to induce a full range of effects. These effects are listed and defined in detail within their own dedicated articles below:

Physical effects Amnesia Disinhibition Dizziness Delusions of sobriety Information processing suppression Motor control loss Muscle relaxation Physical euphoria Thought deceleration Seizure suppression Sedation - In terms of energy level alterations, this drug has the potential to be extremely sedating and often results in an overwhelmingly lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness. Paradoxical effects Paradoxical reactions to benzodiazepines such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%). These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.

Cognitive effects Anxiety suppression Amnesia Compulsive redosing Disinhibition Information processing suppression Thought deceleration Information processing suppression Emotion suppression - Although this compound primarily suppresses anxiety, it also dulls other emotions in manner which is distinct but less intensive than that of antipsychotics. Delusions of sobriety - This is the false belief that one is perfectly sober despite obvious evidence to the contrary such as severe cognitive impairment and an inability to fully communicate with others. It most commonly occurs at heavy dosages.

Pharmacological classes

Benzodiazepines Alprazolam Clonazepam Clonazolam Diazepam Diclazepam Flubromazolam Flubromazepam Nifoxipam Lorazepam Phenazepam Pyrazolam Temazepam

Thienzodiazepines Deschloroetizolam Etizolam Metizolam

Equivalent dosages

The dosages below represent approximate equivalent dosages between various benzodiazepines in comparison to 40mg of diazepam.

The authors of this table specifically state that their equivalents differ from those used by other authors and "are firmly based on clinical experience during switch-over to diazepam at start of withdrawal programs but may vary between individuals."

Prescription benzodiazepines Half-life (Hours) [active metabolite] Approx. equivalent oral dosage (mg) Predominant effect (a= anxiolytic, c= anticonvulsant, h= hypnotic) Alprazolam 6-12 0.5 a Bromazepam 10-20 5-6 a Chlordiazapoxide 5-30 [36-200] 25 a Clobazam 12-60 20 a, c Clonazepam 18-50 0.5 a, c Clorazepate 20-179 [36-200] 15 a Diazepam 20-100 [36-200] 10 a Estazolam 10-24 1-2 h Etizolam 4-12 1 h Flunitrazepam 18-36 [36-200] 1 h Halazepam 14 [30-200] 20 a Ketazolam 30-100 [36-200] 15-30 a Loprazolam 6-12 1-2 h Lorazepam 10-20 1 a Lormetazepam 10-12 1-2 h Medazepam 36-200 10 a Nitrazepam 15-38 10 h Nordazepam 36-200 10 a Oxazepam 4-15 20 a Prazepam 29-224 [36-200] 10-20 a Quazepam 25-100 20 h Temazepam 8-22 20 h Triazolam 2 0.5 h

Research chemicals Half-life (Hours) [active metabolite] Approx. equivalent oral dosage (mg) Predominant effect (a= anxiolytic, c= anticonvulsant, h= hypnotic) Clonazolam ? 0.5 h Deschloroetizolam ~9-20 6 h Desmethyletizolam ~9-20 2 h Diclazepam ~120 1 a Flubromazepam 106 4 h Flubromazolam ? 0.25 h Nifoxipam 4-6 2 a Meclonazepam ? 5 a, c Phenazepam 60 1 a Pyrazolam 17 1 a

Z-drugs Half-life (Hours) [active metabolite] Approx. equivalent oral dosage (mg) Predominant effect (a= anxiolytic, c= anticonvulsant, h= hypnotic) Zaleplon 2 20 h Zolpidem 2 20 h Zopiclone 5-6 15 h Eszopiclone 6 3 h

Toxicity and harm potential

Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.

Benzodiazepines have a low toxicity relative to dose. However, they are [[Toxicity::potentially lethal when mixed with depressants like alcohol or opioids]].

It is strongly recommended that one use harm reduction practices when using this class of compounds.

Tolerance and addiction potential

Benzodiazepines are extremely physically and psychologically addictive.

Tolerance will develop to the sedative-hypnotic effects within a couple of days of continuous use. After cessation, the tolerance returns to baseline in 7-14 days. Withdrawal symptoms or rebound symptoms may occur after ceasing one's usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction.

Discontinuation

Benzodiazepine discontinuation is notoriously difficult; it is potentially life-threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is also an increased risk of hypertension, seizures, and death. Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal.

It is safest to reduce the dose each day by a very small amount, for a couple of weeks until close to abstinence. If using a short half-life benzodiazepine, a longer acting variety such as diazepam can be substituted. Symptoms may still be present, but their severity will be reduced significantly. For more information on tapering from benzodiazepines in a controlled manner, please see this guide. Small amounts of ethanol can also help to reduce the symptoms.

The duration and severity of withdrawal symptoms depends on a number of factors including the half-life of the drug used, tolerance and the duration of abuse. Major symptoms will usually start within just a few days after discontinuation and persist for around a week for shorter lasting benzodiazepines. Benzodiazepines with longer half-lives will exhibit withdrawal symptoms with a slow onset and extended duration.

See also

• Responsible use
• Psychoactive substance index
• Depressants

External links

• Benzodiazepines (Wikipedia)
• Benzodiazepines (Drugs.com)
• Understanding Benzodiazepines by Steven M. Juergens MD