Kanna

Kanna is the common name for Sceletium tortuosum (syn. Mesembryanthemum tortuosum), a low-growing succulent plant of the family Aizoaceae, native to the semi-arid Cape Provinces of South Africa. The San and Khoikhoi peoples have used the plant for millennia as a masticatory — chewing the dried, fermented material (known as kougoed or kauwgoed) to elevate mood, suppress hunger and thirst during long hunts, relieve anxiety, and serve as a social and spiritual sacrament. The first European written record of kanna use dates to 1662, noted by Jan van Riebeeck; by the 18th century it was a significant trade commodity in southern Africa's precolonial exchange economy.

Today kanna is commercially available worldwide as dried plant material, powdered herb, standardised extracts (e.g. Zembrin®, Trimesemine™), tinctures, and capsules. It is consumed orally, sublingually, insufflated as snuff, or occasionally smoked.

Chemistry

Sceletium tortuosum contains 1–1.5% total alkaloids by dry weight, with more than 25 individual compounds identified across four structural classes: mesembrine-type (dominant), Sceletium A4-type, joubertiamine-type, and tortuosamine-type. The principal active alkaloids are:

• Mesembrine — 0.3% in roots, 0.86% in aerial parts; the major psychoactive constituent
• Mesembrenone (Δ⁷-mesembrenone) — dominant in fermented preparations; converted from mesembrine by sunlight and aqueous conditions
• Mesembrenol — present in smaller quantities
• Tortuosamine — minor but pharmacologically active alkaloid

Traditional fermentation transforms mesembrine into mesembrenone while reducing oxalate content (3.6–5.1% in raw material, similar to spinach) — the result is a safer preparation with an altered, reportedly more psychoactive alkaloid profile. Unfermented material contains more total alkaloids but lower bioavailability; fermented extracts show enhanced permeation across buccal and intestinal mucosa.

Pharmacology

Kanna exhibits a dual pharmacological mechanism that distinguishes it from most classical psychoactives:

1. Serotonin reuptake inhibition (SRI) — mesembrine potently inhibits the serotonin transporter (SERT), with an IC₅₀ of approximately 1.4 nM for pure mesembrine. A standardised ethanolic extract shows SERT IC₅₀ of 4.3 µg/mL.
2. Monoamine release — high-mesembrine extracts (Trimesemine™) upregulate vesicular monoamine transporter-2 (VMAT2), promoting the release of serotonin, dopamine and noradrenaline from synaptic vesicles. VMAT2-mediated monoamine release is now considered the primary mechanism behind kanna's acute mood-elevating effects, with SRI as a secondary action.

Additional pharmacological activities include:

• PDE4 inhibition — IC₅₀ of 8.5 µg/mL for a standardised extract; relevant to anti-inflammatory, anxiolytic, and pro-cognitive effects
• Acetylcholinesterase (AChE) inhibition — mild; fermented and unfermented extracts show greater activity than mesembrine alone, suggesting synergistic alkaloid contributions
• CB1 receptor blockade — endocannabinoid modulation; CB1 receptors co-localise with SERT and mediate serotonin release
• Mild MAO-A inhibition — weak but present; adds to the serotonergic load and explains some interaction risk
• CYP17A1 inhibition — modulates glucocorticoid, mineralocorticoid and androgen production, potentially relevant to stress response

Oral bioavailability is moderate; sublingual/buccal absorption is notably higher due to direct mucosal uptake of the alkaloids. Insufflation provides the most rapid onset but also the shortest duration.

Effects

At low-to-moderate doses, kanna acts primarily as a stimulant-empathogen:

• Mood lift, gentle euphoria, increased sociability and empathy
• Enhanced sensory appreciation (music, touch)
• Anxiolysis and stress reduction
• Appetite and thirst suppression
• Mild cognitive sharpening (some clinical trials show improved executive function and set flexibility)

At higher doses, the profile shifts decidedly towards sedation:

• Pronounced sedation, drowsiness, and heavy relaxation
• Possible nausea, dizziness, and headache
• Reduced motor coordination
• Altered perception of time (though not hallucinogenic in the classical sense)

Subjective reports frequently compare the empathogenic peak of kanna to a milder, shorter MDMA experience — an impression consistent with its dual SRI + monoamine-releasing pharmacology. However, kanna lacks the strong dopaminergic and noradrenergic push of MDMA, resulting in a more gentle and controlable experience.

Harm Reduction

• Serotonin syndrome is the primary pharmacological risk. The combination of SRI + monoamine-releasing activity means that any additional serotonergic load can push towards toxicity. MAOIs, SSRIs/SNRIs, tramadol, and MDMA are the most dangerous co-administrations.
• Extracts vs. raw plant: a "50×" extract contains roughly 50 times the alkaloid concentration of raw plant material by weight. Treating extract dosages as interchangeable with raw plant dosages is a common cause of unexpectedly intense effects.
• Cardiovascular considerations: kanna can modestly raise heart rate and blood pressure. People with cardiac disease, uncontrolled hypertension or arrhythmia should exercise caution.
• Chronic use: animal studies show no toxic effects at doses up to 5,000 mg/kg/day in rats over 14 days. No physical dependence or withdrawal syndrome has been documented in humans upon discontinuation. However, daily use can lead to psychological habituation.
• Toxicology: the safety profile in animal models is favourable (NOAEL of 71.4 mg/kg in 90-day rat studies). Oxalate content in raw material (3.6–5.1%) is comparable to spinach or kale and is largely mitigated by fermentation.
• Misidentification: unlike many psychoactive substances, kanna has a low risk of adulteration because it is widely cultivated and inexpensive. However, extract potency varies enormously between vendors — always start with a small test dose from any new batch.

Related Compounds

• Mesembrine — the principal alkaloid; also found in other Sceletium species (S. emarcidum, S. expansum)
• Zembrin® — a patented standardised extract of S. tortuosum (standardised to 0.4% total alkaloids for the four main mesembrine-type alkaloids), used in most published clinical trials
• Trimesemine™ — a high-mesembrine extract studied for its monoamine-releasing properties
• MDMA — shares the empathogenic-style subjective profile, but via very different primary mechanisms (direct serotonin release vs. SRI + vesicular release)
• Kratom (Mitragyna speciosa) — another traditional plant with dose-dependent stimulant-to-sedative pharmacology, though acting via opioid and adrenergic receptors rather than serotonergic ones