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Clobazam

Clobazam molecule structureClobazam molecule structure
Clobazam
Onfi, Sympazan, Frisium, Urbanol, Castilium

Clobazam is a long-acting benzodiazepine derivative belonging to the unique 1,5-benzodiazepine subclass, distinguishing it from the more common 1,4-benzodiazepines.citation needed First synthesized in 19661 and patented in 1968, it was initially marketed as an anxiolytic before gaining approval for epilepsy treatment in 1984.citation needed Clobazam demonstrates a more favorable side-effect profile than older benzodiazepines, with notably less sedation and memory impairment, and shows a distinct addictive potential compared to its 1,4-benzodiazepine counterparts.

Dosage & Duration

Dosage

Doses are population estimates that vary widely between individuals.

Threshold~5 mg
Light5-10 mg
Moderate10-25 mg
Strong25-40 mg
Heavy40+ mg
Bioavailability
~100%

20mg of Clobazam is approximately equal to 10mg of Diazepam

Duration

Onset20-40 minutes
After Effects1-12 hours
Total6-12 hours
Half-life
36-42 hours

Subjective Effects

Legacy content. A statistically backed ontology from Mindstate Design Labs is coming soon.

Clobazam is a long-acting 1,5-benzodiazepine whose effects centre on anxiolysis, with sedation reported as less pronounced than that of older 1,4-benzodiazepines at comparable doses. Its unfavourable side-effect profile relative to other benzodiazepines means it is not often taken recreationally. At higher doses or in overdose the experience shifts toward drowsiness, confusion and impaired coordination, with amnesia and other cognitive impairments persisting even as tolerance develops to other effects.

Physical

Muscle relaxation and sedation are the main physical effects, accompanied at higher doses by unsteady coordination, slurred speech and lethargy.

Coordination

Sedation

Uncomfortable

Cognitive

The headspace is primarily one of reduced anxiety, though impaired concentration, memory disruption and confusion are documented, and euphoria and disinhibition are reported in the context of misuse.

Disconnective

Emotional

Impairment

Suppressions

Visual

Pharmacology

Pharmacodynamics

Clobazam is a 1,5-benzodiazepine that acts as a positive allosteric modulator at the GABA-A receptor, binding at the benzodiazepine site to potentiate GABAergic neurotransmission.2 This binding increases chloride conductance in neurons, causing hyperpolarization that raises the action potential threshold and reduces neuronal firing frequency, thereby depressing central nervous system activity.citation needed Clobazam demonstrates higher affinity for the α2 subunit of the GABA-A receptor, which mediates anxiolytic effects, compared to the α1 subunit responsible for sedation.2 This subunit selectivity, along with its proposed partial agonist activity rather than full agonism, may account for its reduced sedative and amnesic effects compared to classical 1,4-benzodiazepines.citation needed Some additional activity at sodium channels and voltage-sensitive calcium channels has been speculated.

Pharmacokinetics

Clobazam is rapidly and extensively absorbed following oral administration, with time to peak concentrations ranging from 0.5 to 4 hours.3 Oral bioavailability is approximately 100% and is unaffected by food.citation needed The drug is lipophilic and distributes rapidly throughout the body with an apparent volume of distribution of approximately 100 L at steady state.3 Clobazam is extensively metabolized in the liver, primarily via N-demethylation catalyzed by CYP3A4 and to a lesser extent by CYP2C19 and CYP2B6, producing the active metabolite N-desmethylclobazam (norclobazam).citation needed Hydroxylation produces 4-hydroxyclobazam, facilitated by CYP2C18 and CYP2C19. N-desmethylclobazam is the major circulating metabolite, reaching plasma concentrations 3 to 5 times higher than the parent compound at therapeutic doses.3 The polymorphic CYP2C19 is the major contributor to N-desmethylclobazam metabolism, with poor metabolizers showing 5-fold higher plasma levels.3 Approximately 82% of the dose is excreted in urine and 11% in feces, with only about 2% recovered as unchanged drug.citation needed

Interactions

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.

1,2-BenzodiazepineAbacavirAbametapirAbataceptAbemaciclib
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Tolerance

Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.

Full Tolerance
Tolerance to the therapeutic and anticonvulsant effects of clobazam develops with continued therapy. The rate of tolerance development varies by effect, while tolerance to seizure control may become clinically significant during long-term prophylactic use, little tolerance develops to the amnestic reactions and other cognitive impairments caused by the drug. This differential tolerance pattern is characteristic of benzodiazepines and may render long-term therapy less effective for epilepsy management.
Cross Tolerance

Benzodiazepines, GABAergic depressants

Harm Potential

Addiction & Dependence

Psychological

High

Clobazam is a benzodiazepine with significant potential for abuse and addiction.citation needed Animal studies have shown increased reward-seeking behaviors, and abuse has been reported internationally. Even therapeutic use may put patients at risk for abuse and misuse, which often involves doses greater than recommended and concomitant use of other substances.3

Physical

High

Physical dependence develops from continued therapy.citation needed Abrupt discontinuation or rapid dose reduction may precipitate acute withdrawal reactions including life-threatening seizures.3 Acute withdrawal symptoms include anxiety, tremor, insomnia, tachycardia, and in severe cases catatonia, convulsions, delirium tremens, hallucinations, and psychosis.3 Protracted withdrawal syndrome may persist for weeks to over 12 months, characterized by anxiety, cognitive impairment, depression, paresthesia, and motor symptoms.3

Toxicity

Hepatic

Use is contraindicated or requires great care in patients with severe liver diseases such as cirrhosis and hepatitis; specific hepatotoxicity from clobazam itself is not well characterized but liver disease significantly affects drug handling.

Dermatological

Serious skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis can occur, particularly within the first eight weeks of treatment.citation needed

Respiratory

Respiratory depression can occur, particularly in overdose or when combined with other CNS depressants; use requires great care in patients with severe respiratory failure or sleep apnea.citation needed

Skeletal

Administration during juvenile development in rats resulted in decreased bone density and bone length at high doses.3

Carcinogenicity
Possible

In rats, oral administration for 2 years resulted in increases in thyroid gland tumors (follicular cell adenoma and carcinoma) and liver tumors (hepatocellular adenoma) at mid and high doses.3

Evidence Basis
Human EpidemiologicalNone
Animal Models
Positive
(rat)

Psychosis Risk

Psychosis may occur as a severe withdrawal symptom during abrupt discontinuation.3 Paradoxical or disinhibitory reactions including agitation, confusion, and excitement may rarely occur during use or overdose.citation needed Hallucinations and delirium tremens have been reported with severe withdrawal.

Seizure Risk

While clobazam is used as an anticonvulsant, abrupt discontinuation or rapid dose reduction can precipitate acute withdrawal seizures which may be life-threatening.3 Tolerance to anticonvulsant effects may develop with continued use, and withdrawal seizures may occur during abrupt or overly rapid withdrawal.citation needed

History & Culture

Discovery and Development

Clobazam was discovered at the Maestretti Research Laboratories in Milan, Italy, with the compound first synthesized in 1966 and first published in 1969.citation needed This development followed the incidental synthesis and discovery of the first benzodiazepine, chlordiazepoxide, in the 1950s.…

Legality

By Country

Controlled / restricted2
India flagIndiaRestricted
Indonesia flagIndonesiaRestricted
Prescription6
United States flagUnited StatesPrescription only
Canada flagCanadaPrescription (Schedule IV)
Germany flagGermanyPrescription only
Singapore flagSingaporePrescription only
Spain flagSpainPrescription only
United Kingdom flagUnited KingdomPrescription only

References

Source Pages

  1. DrugBank
  2. DrugBank Article: Clobazam for Lennox-Gastaut syndrome
  3. DrugBank: Clobazam Pharmacology
  4. Erowid: Clobazam Vault
  5. TripSit: Drug Combination Chart
  6. Wikipedia

Citations

  1. Kyriakopoulos CE, & Bhattarai S. (n.d.). Clobazam - StatPearls. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK541043/12
  2. Angela C. Gauthier, & Richard H. Mattson. (July 2015). Clobazam: A Safe, Efficacious, and Newly Rediscovered Therapeutic for Epilepsy. CNS Neuroscience & Therapeutics, 21(7), 543–548. https://doi.org/10.1111/cns.1239912
  3. Onfi- clobazam tablet; Onfi- clobazam suspension. DailyMed (12 March 2024). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de03bd69-2dca-459c-93b4-541fd3e9571c1234567891011121314
  4. TEVA-CLOBAZAM Product Information (DIN 02238334) - Health Canada Drug Product Database. (n.d.). https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=617401
  5. Betäubungsmittelgesetz (BtMG), Anlage III (zu § 1 Abs. 1). gesetze-im-internet.de (n.d.). https://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html1
  6. Betäubungsmittelgesetz (BtMG), Anlage III (zu § 1 Abs. 1). gesetze-im-internet.de (n.d.). https://www.gesetze-im-internet.de/btmg_1981/__1.html1
  7. Betäubungsmittelgesetz (BtMG), Anlage III (zu § 1 Abs. 1). gesetze-im-internet.de (n.d.). https://www.gesetze-im-internet.de/btmg_1981/__13.html1
  8. Narcotic Drugs and Psychotropic Substances Act, 1985, Schedule. cbn.gov.in (n.d.). https://www.cbn.gov.in/pdf/exim/SchPSAct.PDF1
  9. Narcotic Drugs and Psychotropic Substances Act, 1985, Schedule. cbn.gov.in (n.d.). https://www.cbn.gov.in/pdf/exim/ControlStatusIM.pdf1
  10. Narcotic Drugs and Psychotropic Substances Act, 1985, Schedule. upload.indiacode.nic.in (n.d.). https://upload.indiacode.nic.in/showfile?actid=AC_CEN_2_2_00029_198561_1517807326222&filename=1996_-_gsr_509_e_04-11-1996.pdf&type=notification1

Further Reading

  1. Drug-Do: Benzos
  2. Epilepsy Foundation: Clobazam Information
  3. MedlinePlus: Clobazam Drug Information
  4. NIH PMC: Clobazam - A Safe, Efficacious, and Newly Rediscovered Therapeutic for Epilepsy
  5. PubChem: Clobazam
  6. TripSit: List of Benzodiazepines

Article Status

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Recent changes8 human edits · latest

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19 August 2026

  1. Lyrea · Reworded 2 words in Tolerance › Full tolerance

  2. Lyrea · Changed a word in Dosage & Duration › Routes 1 › Notes

  3. Lyrea · Changed a word in Dosage & Duration › Routes 1 › Dose ranges › Strong

  4. Lyrea · Changed a word in Dosage & Duration › Routes 1 › Dose ranges › Moderate

  5. Lyrea · Changed a word in Dosage & Duration › Routes 1 › Dose ranges › Moderate

  6. Lyrea · Changed a word in Dosage & Duration › Routes 1 › Dose ranges › Strong

  7. Lyrea · Changed a word in Dosage & Duration › Routes 1 › Dose ranges › Heavy

  8. Lyrea · Changed a word in Dosage & Duration › Routes 1 › Dose ranges › Heavy

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