Tetrahydrocannabinol/cannabinol/cannabidiol
 | |
 | |
| Combination of | |
|---|---|
| Tetrahydrocannabinol | Cannabinoid |
| Cannabinol | Cannabinoid |
| Cannabidiol | Cannabinoid |
| Clinical data | |
| Trade names | Zenivol |
| Other names | THC/CBN/CBD; ZTL-101; ZTL101 |
| Routes of administration | Sublingual |
| Drug class | Cannabinoids; Cannabinoid receptor modulators |
Tetrahydrocannabinol/cannabinol/cannabidiol (THC/CBN/CBD), sold under the brand name Zenivol and also known by its developmental code name ZTL-101, is a cannabinoid medication used for the treatment of insomnia. It is approved and marketed in Germany.[1]
Medical uses
[edit]THC/CBN/CBD is indicated for the management of insomnia. Clinical trials have shown that it improves time to sleep, reduces nighttime awakenings, increases total sleep time, and enhances sleep quality and feeling refreshed after sleep.[2][3][4]
Available forms
[edit]The drug is administered sublingually as a liquid using a syringe about 1 hour before bedtime.[1][3][4] Each 0.5 mL dose contains 10 mg δ9-tetrahydrocannabinol (THC), 1 mg cannabinol (CBN), and 0.5 mg cannabidiol (CBD), corresponding to a 20:2:1 mg/mL ratio.[2][3][4] One or two doses are typically taken per night.[4]
Adverse effects
[edit]Reported side effects are generally mild and resolve upon waking.[2][3][4] They include dry mouth, dizziness, headache, and "feeling abnormal".[2][3][4]
Pharmacology
[edit]Pharmacokinetics
[edit]The pharmacokinetics of the formulation have been investigated and described in clinical studies.[4]
Pharmacodynamics
[edit]THC is a psychoactive cannabinoid acting as a CB1 and CB2 receptor partial agonist. CBN is a mildly psychoactive cannabinoid that also acts as a CB1 and CB2 receptor partial agonist. CBD does not act as an agonist at cannabinoid receptors but modulates the endocannabinoid system and other molecular targets.[2][4][5][6] THC/CBN/CBD does not significantly alter sleep architecture, aside from a near-significant 3.5% reduction in REM sleep duration.[2][4]
History
[edit]THC/CBN/CBD was approved and launched as a pharmaceutical drug for insomnia in Germany in 2022.[1] It was developed and is marketed by Zelira Therapeutics.[1]
See also
[edit]References
[edit]- ^ a b c d "Cannabidiol/tetrahydrocannabinol". AdisInsight. 25 July 2022. Retrieved 1 October 2025.
- ^ a b c d e f Maddison KJ, Kosky C, Walsh JH (2022). "Is There a Place for Medicinal Cannabis in Treating Patients with Sleep Disorders? What We Know so Far". Nature and Science of Sleep. 14: 957–968. doi:10.2147/NSS.S340949. PMC 9124464. PMID 35611178.
- ^ a b c d e Lavender I, McGregor IS, Suraev A, Grunstein RR, Hoyos CM (August 2022). "Cannabinoids, Insomnia, and Other Sleep Disorders". Chest. 162 (2): 452–465. doi:10.1016/j.chest.2022.04.151. PMID 35537535.
The most robustly designed study to date examined the safety and efficacy of the cannabinoid formulation ZTL101 (D9-THC 10 mg, CBN 1 mg, and CBD 0.5 mg) relative to placebo in a sample of 23 patients with chronic insomnia disorder.11 Participants self-administered ZTL-101 one hour prior to bedtime for 2 weeks, with the option to double the dose after the fourth night (52% of participants increased the dose). ZTL-101 improved subjective sleep quality by 5.1 points (95% CI, –7.3 to –2.9) on the Insomnia Severity Index and improved self-reported sleep-onset latency, total sleep time, subjective sleep quality, and feelings of rest upon waking. Actigraphy measures indicated reduced wake following sleep onset and increased total sleep time; however, no differences in polysomnography indexes were observed.11 Headaches, xerostomia, dizziness, and "feeling abnormal" were reported more frequently with active treatment (n = 17) than with placebo (n = 4), but these adverse events were self-limiting and did not persist upon wake.
- ^ a b c d e f g h i Walsh JH, Maddison KJ, Rankin T, Murray K, McArdle N, Ree MJ, et al. (November 2021). "Treating insomnia symptoms with medicinal cannabis: a randomized, crossover trial of the efficacy of a cannabinoid medicine compared with placebo". Sleep. 44 (11) zsab149. doi:10.1093/sleep/zsab149. PMC 8598183. PMID 34115851.
- ^ Sampson PB (January 2021). "Phytocannabinoid Pharmacology: Medicinal Properties of Cannabis sativa Constituents Aside from the "Big Two"". Journal of Natural Products. 84 (1): 142–160. doi:10.1021/acs.jnatprod.0c00965. PMID 33356248.
- ^ Britch SC, Babalonis S, Walsh SL (January 2021). "Cannabidiol: pharmacology and therapeutic targets". Psychopharmacology. 238 (1): 9–28. doi:10.1007/s00213-020-05712-8. PMC 7796924. PMID 33221931.