Clonazepam

5-(2-chlorophenyl)-7-nitro-1,3-dihydro-2H-1,4-benzodiazepin-2-one

Klonopin, Rivotril, K-Pin, K, Pin

Psychoactive Class

Depressant Anxiolytic Anticonvulsant GABAergic Muscle Relaxant Sedative

Chemical Class

Clonazepam is a long-acting benzodiazepine¹ that produces primarily anxiolytic effects alongside anticonvulsant¹, sedative, muscle relaxant, and hypnotic properties. Patented in 1960 and first marketed in the United States by Roche in 1975, it is widely prescribed for the treatment of panic disorder², anxiety disorders, and seizures². Now available as a generic medication, it remains one of the most commonly prescribed benzodiazepines, with millions of prescriptions written internationally each year.

Dosage & Duration

Dosage

Threshold~0.1 mg

Light0.25-0.5 mg

Moderate0.5-1 mg

Strong1-2 mg

Heavy2+ mg

Bioavailability

~90%

Duration

Onset20-60 minutes

Peak2-4 hours

Offset3-6 hours

After Effects8-48 hours

Total8-12 hours

Half-life

19-60 hours

Subjective Effects

Effects vary widely by individual, dose, and context.

Physical

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

Dizziness Muscle relaxation Physical euphoria Motor control loss Respiratory depression Seizure suppression

Cognitive

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

Amnesia Anxiety suppression Thought deceleration Disinhibition Information processing suppression Euphoria Compulsive redosing

Forked from Subjective Effect Documentation

by Josie KinsSeptember 2015.

Reagent Testing

Loading reagent data

Expected colorimetric results are being prepared.

Pharmacology

Pharmacodynamics

Clonazepam acts as a positive allosteric modulator at the benzodiazepine binding site on GABA-A receptors, enhancing GABAergic inhibition by increasing the opening frequency of chloride ion channels.³ This produces hyperpolarization of neuronal cell membranes and reduces excitability. Clonazepam has also been shown to decrease serotonin utilization by neurons and to inhibit depolarization-sensitive calcium uptake via micromolar benzodiazepine binding sites.

Pharmacokinetics

Clonazepam is absorbed rapidly after oral administration with an absolute bioavailability of approximately 90%.⁴ It is metabolized extensively in the liver, primarily through nitroreduction catalyzed by CYP3A4.⁴³ The major metabolic pathways include reduction of the nitro group to an amine, N-acetylation, and hydroxylation at the C-3 position.⁴ The resulting metabolites are pharmacologically inactive. The elimination half-life ranges from 19 to 60 hours.

Interactions

Dangerous

Highest risk

These combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.

AlcoholGHB/GBLOpioidsTramadol

Unsafe

Avoid

There is considerable risk of physical harm when taking these combinations, they should be avoided where possible.

DiphenhydraminePCP

Caution

Use caution

These combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.

DXMKetamineMXE

TripSit

Tolerance

Full Tolerance

Tolerance to sedative-hypnotic effects can emerge quickly, often after only several days of uninterrupted use. Tolerance to anticonvulsant effects may also develop with prolonged administration.

Baseline Reset

Typically returns to baseline within 7-14 days following cessation, although individuals with extended histories of regular use may require considerably longer periods for complete tolerance reset.

Half Tolerance

7-14 days after cessation of use, though this may take significantly longer in cases of prolonged or intensive use.

Cross Tolerance

All benzodiazepines, Other GABAergic depressants (barbiturates, alcohol)

Harm Potential

Addiction & Dependence

Psychological

Extremely High

Extremely high psychological addiction potential. Dependence develops in approximately one-third of individuals who take benzodiazepines for longer than four weeks.⁵ The U.S. FDA mandates boxed warnings describing risks of abuse, misuse, and addiction for all benzodiazepine medications.⁶

Physical

Extremely High

Physical dependence develops readily with regular use, and discontinuation can be life-threatening.⁶ Withdrawal symptoms include anxiety, irritability, insomnia, tremors, sweating, confusion, and hallucinations.⁶ Severe withdrawal may cause seizures comparable to delirium tremens.⁷⁶ Gradual tapering over weeks to months is essential for safe discontinuation.⁶

Psychosis Risk

Psychosis is a rare adverse effect during use, with paradoxical reactions including hallucinations occurring in less than 1% of the general population.⁶ Risk is elevated in recreational abusers, individuals with mental disorders, children, and those on high-dosage regimens. Psychosis can also occur during severe withdrawal, characterized by dysphoric manifestations, aggressiveness, anxiety, and hallucinations.⁶

Seizure Risk

Although clonazepam is an anticonvulsant, paradoxical increases in seizure frequency can occur at supratherapeutic plasma concentrations. Critically, abrupt discontinuation after regular use can induce potentially life-threatening seizures including status epilepticus.⁶ Gradual dose tapering is essential to prevent withdrawal-related seizures.⁶

History & Culture

Clonazepam was patented in 1960 and first marketed in 1964 before being released for sale in the United States by Roche in 1975.⁸ The medication was subsequently approved as a generic drug in the United States in 1997 and is now manufactured and marketed by multiple…

Legality

International

1961 Single Convention: clonazepam is not scheduled.

1971 Convention on Psychotropic Substances: Schedule IV.

1988 Convention: clonazepam is not listed in precursor Tables I or II.

By Country

United StatesPrescription onlySchedule IV controlled prescription

21 CFR § 1308.14(c)¹⁵

Current official law controls clonazepam while permitting regulated prescription medical use in United States.

BrazilBlack Stripe (Tarja Preta)Citation needed

Classified as a controlled medication requiring special prescription protocols. The black stripe designation indicates heightened regulatory control due to dependence potential.

Czech RepublicSchedule IV (List 7)Citation needed

Controlled under Government Regulation 463/2013. Dispensed by prescription without requiring the blue stripe designation used for more strictly controlled substances.

IndiaSchedule HCitation needed

Prescription-only medication under the Drugs and Cosmetics Rules. Sale without a valid prescription from a registered medical practitioner is prohibited.

NetherlandsList II (Opiumwet)Citation needed

Controlled under the Opium Act. Available only by prescription for medical use. Preparation, distribution, and transport without authorization are prohibited, though possession of small quantities for personal use is typically not prosecuted.

NorwayClass B / P IVCitation needed

Designated as a narcotic substance in prescription category IV. Possession without a valid prescription constitutes an offense under Norwegian drug legislation.

SwitzerlandVerzeichnis BCitation needed

Listed in Schedule B of controlled substances under Swiss narcotics legislation. Medicinal use is permitted with appropriate prescription.

United KingdomPrescription onlyClass C · Schedule 4 Part I

Misuse of Drugs Act 1971; Misuse of Drugs Regulations 2001¹⁴

Current official law controls clonazepam while permitting regulated prescription medical use in United Kingdom.

AustraliaPrescription Only (S4)Citation needed

Available exclusively through medical prescription. Unauthorized possession or supply constitutes an offense under state and territory drugs legislation.

CanadaPrescription onlySchedule IV controlled prescription

Controlled Drugs and Substances Act, Schedule IV¹¹

Current official law controls clonazepam while permitting regulated prescription medical use in Canada.

GermanyPrescription onlyAnlage III controlled prescription

Betäubungsmittelgesetz, Anlage III¹²

Current official law controls clonazepam while permitting regulated prescription medical use in Germany.

IsraelPrescription OnlyCitation needed

Available exclusively through medical prescription. Subject to controlled substance regulations governing benzodiazepine medications.

New ZealandSchedule 3 (Class C)Citation needed

Controlled drug under the Misuse of Drugs Act 1975.¹³ Requires prescription for lawful possession and is subject to restrictions on manufacturing and distribution.

RussiaSchedule IIICitation needed

Listed as a controlled substance in Schedule III since April 2013. Subject to strict prescription requirements and regulatory oversight.

TurkeyGreen PrescriptionCitation needed

Requires the special green prescription form reserved for controlled medications. Possession or sale without valid prescription documentation is prohibited.

References

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Citations

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