Limited evidenceStress & mood

Kanna (Sceletium)

Genuinely interesting pharmacology - kanna's alkaloids inhibit serotonin reuptake and PDE4 - but the entire human evidence base is three tiny studies totalling under 80 people. Treat it as experimental, and never combine it with serotonergic medication.

What the science says

Reduces threat-related brain activity Limited evidence
In a double-blind, placebo-controlled crossover pharmaco-fMRI study, 16 healthy participants received a single 25 mg dose of the standardized extract Zembrin. Amygdala reactivity to fearful faces under low perceptual load was attenuated, and amygdala-hypothalamus connectivity was reduced. This is a mechanistic finding consistent with anxiolytic potential, not a clinical outcome in anxious patients.
Cognitive flexibility and executive function Limited evidence
A randomized double-blind placebo-controlled crossover study gave 21 cognitively healthy adults (mean age 54.6) 25 mg/day of Zembrin or placebo for 3 weeks each. Cognitive set flexibility (p = 0.032) and executive function (p = 0.022) improved on CNS Vital Signs testing, with reported positive changes in mood and sleep. The authors labelled it explicitly a proof-of-concept study.
Short-term tolerability Moderate evidence
A 3-month randomized, double-blind, parallel-group trial in 37 healthy adults at 8 mg or 25 mg daily found no meaningful differences from placebo in vital signs, 12-lead ECG, body weight, haematology, biochemistry or urinalysis. Headache was the most common adverse event and occurred more often on placebo than on kanna.

Dosage & safety

Studied doseStandardized extract of the Zembrin type (roughly 0.35-0.45% total alkaloids): 8-25 mg once daily, which is the only dosing tested in controlled trials. Raw fermented plant material is commonly sold at 50-200 mg or more, but is unstandardized and its mesembrine alkaloid content varies enormously between products.

SafetyAt 8-25 mg/day for 3 months, tolerability was comparable to placebo on objective measures. The serious concern is pharmacological: mesembrine and related alkaloids are serotonin reuptake inhibitors and PDE4 inhibitors, so kanna should not be combined with SSRIs, SNRIs, tricyclics, MAOIs, triptans, tramadol, lithium or St John's wort - serotonin syndrome is a plausible risk and there is no human interaction data at all. Reported effects include headache, appetite loss, and anxiety or irritability at higher doses; unstandardized raw material has caused sedation, nausea and dysphoria. Nothing is known about use beyond 3 months, in pregnancy, in children, or in people with psychiatric illness.

Scientific references

A randomized, double-blind, parallel-group, placebo-controlled trial of Extract Sceletium tortuosum (Zembrin) in healthy adults
Nell H, Siebert M, Chellan P, Gericke N — J Altern Complement Med, 2013
Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer's Dementia
Chiu S, Gericke N, Farina-Woodbury M, et al. — Evid Based Complement Alternat Med, 2014
Acute effects of Sceletium tortuosum (Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala and its connection to the hypothalamus
Terburg D, Syal S, Rosenberger LA, et al. — Neuropsychopharmacology, 2013

Where to buy

Protocol for Life Balance, Sceletium Extract, 60 Veg Capsules

View on iHerb

Referral link — this site may earn a commission on purchases.

Related in Stress & mood

Ashwagandha Moderate evidence
L-Methylfolate Limited evidence
5-HTP Limited evidence
L-Ornithine Limited evidence
SAM-e Moderate evidence
Rhodiola Rosea Limited evidence