Lorazepam

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.

Lorazepam
Chemical Nomenclature
Common names	Lorazepam, Ativan, Orfidal, Lorsilan
Substitutive name	Lorazepam
Systematic name	(RS)-7-Chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-2H-1,4-benzodiazepin-2-one
Class Membership
Psychoactive class	Depressant
Chemical class	Benzodiazepine
Routes of Administration
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. ⇣ Oral Dosage Threshold 0.10 mg Light 0.25 - 0.5 mg Common 0.5 - 1.5 mg Strong 1.5 - 2 mg Heavy 2 - 3 mg + Duration Total 4 - 8 hours Onset 5 - 30 minutes Peak 1 - 3 hours Offset 4 - 8 hours DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Interactions

Summary sheet: Lorazepam

Lorazepam (trade name Ativan) is an intermediate-duration psychoactive drug of the benzodiazepine class which produces anxiolytic, sedative, hypnotic, muscle relaxant, anticonvulsant, anti-nausea and amnestic effects. Lorazepam, like other benzodiazepines, binds to specific sites on the GABA_A gamma-amino-butyric acid receptor. Lorazepam is used for the short-term treatment of anxiety, insomnia, acute seizures, and the sedation of hospitalized patients.

Sudden 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

Lorazepam is a drug of the benzodiazepine class. Benzodiazepine drugs contain a benzene ring fused to a diazepine ring, which is a seven membered ring with the two nitrogen constituents located at R₁ and R₄. Further, the benzodiazepine ring is bonded at R₅ to a 2-chlorinated phenyl ring. R₇ of the benzyl ring is also substituted with a chlorine group. Additionally, Lorazepam contains a hydroxy (OH-) group substituted at R₃. It also contains an oxygen group double bonded to R₂ of its diazepine ring to form a ketone. This oxygen substitution at R₂ is shared with other benzodiazepine drugs with the suffix -azepam.

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 within the brain, its modulation results in the sedating (or calming effects) of lorazepam on the nervous system.

Relative to other benzodiazepines, lorazepam is thought to have high affinity for GABA receptors, which may also explain its marked amnesic effects. The anticonvulsant properties of lorazepam and other 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.

Physical effects

The physical effects of lorazepam can be broken down into several components which progressively intensify proportional to dosage.

These are described below and generally include:

• 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.
• Motor control loss
• Muscle relaxation
• Dizziness
• Respiratory depression
• Seizure suppression

Cognitive effects

The cognitive effects of lorazepam can be broken down into several components which progressively intensify proportional to dosage. The general head space of lorazepam is described by many as one of intense sedation and decreased inhibition. It contains a large number of typical depressant cognitive effects.

The most prominent of these cognitive effects generally include:

• Anxiety suppression
• Thought deceleration
• Disinhibition
• Information processing suppression
• Amnesia
• Compulsive redosing
• 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.

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.

Toxicity and harm potential

Main article: Research chemicals § Toxicity and harm potential

Lethal dosage

The acute oral LD50 in mice is 1850 mg/kg; however, (like many benzodiazepines) it has a large therapeutic index and margin of safety. As with all GABAergic drugs, overdose can be lethal when mixed with other depressants including alcohol or opioids.

It is strongly recommended that one use harm reduction practices when using this drug.

Tolerance and addiction potential

Tolerance to benzodiazepine effects develops with regular use. This is desirable with the amnesic and sedative effects, but undesirable with the anxiolytic, hypnotic, and anticonvulsant effects. After four to six months of regular benzodiazepine use, evidence of continued efficacy declines. If regular treatment is continued for longer than this, dose increases may be necessary to maintain effects.

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 seizure following discontinuation of benzodiazepines. Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal.

Dangerous interactions

Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

• Depressants (1,4-Butanediol, 2-methyl-2-butanol, alcohol, barbiturates, GHB/GBL, methaqualone, opioids) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances also potentiate the muscle relaxation, sedation and amnesia caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
• Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
• Stimulants - It is dangerous to combine benzodiazepines with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of benzodiazepines, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of benzodiazepines will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only dosing a certain amount of benzodiazepines per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.

Legal issues

• International: The drug is a Schedule IV drug under the United Nations Convention on Psychotropic Substances.
• United States: Lorazepam is a Schedule IV drug under the Controlled Substances Act in the U.S.
• Canada: It is a Schedule IV drug under the Controlled Drugs and Substances Act in Canada.
• United Kingdom: It is a Class C, Schedule 4 controlled drug under the Misuse of Drugs Regulations 2001.

Preparation methods

Preparation methods for this compound within our preparation index include:

• Volumetric liquid dosing

See also

• Responsible use
• Psychoactive substance index
• Etizolam
• Benzodiazepines
• Depressants
• Volumetric liquid dosing

External links

• Lorazepam (Erowid)
• Lorazepam experiences (Erowid)
• Lorazepam (Wikipedia)