Peer-reviewed papers, curated.

Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T · Phytotherapy Research

Hericium erinaceus is a culinary and medicinal mushroom containing hericenones with documented nerve-growth-factor (NGF) inducing activity in vitro. This double-blind placebo-controlled trial enrolled 30 Japanese adults aged 50-80 with mild cognitive impairment. Subjects received 3×250 mg of lion's mane powder three times daily for 16 weeks, followed by 4 weeks of washout. Cognitive function (Hasegawa Dementia Scale) improved significantly in the treatment group during the 16-week dosing period. The improvement diminished within 4 weeks of discontinuation, suggesting the effect requires continued exposure.

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Kawagishi H, Ando M, Sakamoto H, Yoshida S, Ojima F, et al. · Tetrahedron Letters

Three novel compounds, hericenones C, D, and E, were isolated from the dried fruit body of Hericium erinaceus. All three induce nerve growth factor (NGF) synthesis in cultured astrocytes at low concentrations. The structural characterization establishes hericenones as a class of cyathane-type diterpenoids; mechanism for NGF induction is consistent with selective signaling-pathway activation rather than direct cytotoxic stress.

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Kawagishi H, Shimada A, Shirai R, Okamoto K, Ojima F, et al. · Tetrahedron Letters

Three novel diterpenoids, erinacines A, B, and C, were isolated from the mycelia of Hericium erinaceum. All three induce nerve growth factor (NGF) synthesis with substantially higher potency than hericenones. The compounds appear concentrated in the mycelial fraction rather than the fruit body, which has implications for product formulation and supplement-industry labeling.

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Wachtel-Galor S, Yuen J, Buswell JA, Benzie IFF · Herbal Medicine: Biomolecular and Clinical Aspects (CRC Press)

Ganoderma lucidum (reishi) is one of the most-studied medicinal mushrooms in the published literature. The two principal active fractions are the polysaccharide complex (β-glucans, immunomodulatory) and the triterpene fraction (ganoderic acids and related lanostane-type compounds, anti-inflammatory and hepatoprotective). Dual-extraction approaches (hot-water + alcohol) are used to capture both fractions in a single preparation. Clinical evidence is strongest for adjuvant immune-modulation use in oncology supportive care.

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Goodridge HS, Wolf AJ, Underhill DM · Immunological Reviews

Beta-glucans from fungal cell walls are recognized by the innate immune system primarily through dectin-1, a C-type lectin expressed on macrophages, dendritic cells, and neutrophils. Dectin-1 binding triggers Syk kinase activation and downstream signaling that induces phagocytosis, reactive-oxygen-species production, and cytokine release including TNF-α, IL-6, IL-10, and IL-23. The β-(1,3)/β-(1,6) glucan structural pattern is the key recognition motif; α-glucans (e.g., starch) are not recognized.

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Pertwee RG · British Journal of Pharmacology

Δ9-THC is a partial agonist at CB1 and CB2 receptors with higher CB1 affinity. CBD has minimal CB1/CB2 affinity at consumer doses; its broader pharmacology includes negative allosteric modulation at CB1, partial agonism at 5-HT1A serotonin receptors, TRPV1 desensitization, and inhibition of fatty-acid amide hydrolase (FAAH). Δ9-THCV behaves as a CB1 antagonist at low doses and a CB2 partial agonist at higher doses. The diversity of receptor profiles across structurally similar cannabinoids underlies the wide range of effects observed clinically.

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Shannon S, Lewis N, Lee H, Hughes S · The Permanente Journal

Retrospective chart review of 72 adult psychiatric patients receiving CBD as adjunctive treatment in an outpatient setting. Anxiety scores decreased in the first month for 79.2% of patients and remained decreased at month 3. Sleep scores improved within the first month for 66.7% of patients but fluctuated over time. CBD was generally well-tolerated; only 3 patients discontinued due to side effects. Findings are consistent with prior preclinical evidence and warrant controlled investigation.

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Englund A, Morrison PD, Nottage J, Hague D, Kane F, et al. · Journal of Psychopharmacology

Double-blind randomized controlled trial in 48 healthy male volunteers comparing pretreatment with 600 mg oral CBD vs placebo before intravenous THC (1.5 mg). CBD pretreatment significantly reduced THC-induced paranoid symptoms and prevented THC-induced hippocampal-dependent memory impairment. The findings provide controlled human evidence for the entourage-effect hypothesis: CBD modulates THC's adverse psychoactive effects without abolishing the psychoactive experience.

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Bagheri H, Manap MYBA, Solati Z · Ultrasonics Sonochemistry

Comprehensive review of ultrasound-assisted extraction (UAE) for bioactive compounds from medicinal mushrooms (Ganoderma, Hericium, Trametes, Pleurotus, Lentinula). UAE produces yield improvements of 20-60% over conventional reflux and Soxhlet extraction across compound classes (β-glucans, triterpenes, phenolics, ergosterol), with extraction time reductions of 50-80%. Key process variables: probe power (typically 100-500 W bench-scale), frequency (20-40 kHz), solvent ratio, particle size, and duty cycle. Cooling jackets are required for thermolabile compounds.

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Chemat F, Rombaut N, Sicaire AG, Meullemiestre A, Fabiano-Tixier AS, Abert-Vian M · Ultrasonics Sonochemistry

Foundational review on UAE for natural-product extraction across food + cosmetic + pharmaceutical applications. Covers the mechanism of acoustic cavitation in detail — bubble nucleation, growth, collapse, and the resulting localized temperature and pressure spikes that drive cell-wall disruption. Compares UAE to conventional reflux, Soxhlet, supercritical CO2, and microwave-assisted extraction across capital cost, operating cost, and product-quality dimensions.

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Russo EB · British Journal of Pharmacology

Comprehensive review of cannabinoid-terpenoid synergy in cannabis. Argues that whole-plant extracts produce different effects than purified single cannabinoids at matched dose, mediated by terpene contributions at non-cannabinoid receptors (5-HT1A, GABA, TRPV1, etc.). The paper is the foundational citation for what marketers call 'the entourage effect'; subsequent controlled work has supported some claims and not others.

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Gertsch J, Leonti M, Raduner S, Racz I, Chen JZ, et al. · Proceedings of the National Academy of Sciences (PNAS)

β-caryophyllene, a sesquiterpene found in cannabis, black pepper, cloves, and rosemary, is shown to be a selective full agonist of the CB2 cannabinoid receptor. This is the only known terpene with direct cannabinoid-receptor activity. CB2 activation produces anti-inflammatory and pain-modulating effects without psychoactive consequence. The finding establishes a mechanistic basis for CB2-mediated effects of caryophyllene-rich plant materials independent of plant cannabinoids.

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Tuli HS, Sandhu SS, Sharma AK · Life Sciences

Cordycepin (3'-deoxyadenosine), produced by Cordyceps militaris and several other entomopathogenic fungi, is structurally similar to adenosine and acts on multiple targets including mTOR signaling, polyadenylation of mRNA, and adenosine receptors. The compound is unstable in plasma due to rapid deamination by adenosine deaminase, which limits oral bioavailability. Co-administration with deaminase inhibitors substantially extends plasma half-life. Therapeutic potential has been investigated in cancer-adjuvant, anti-inflammatory, and metabolic contexts.

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Szigeti B, Kartner L, Blemings A, Rosas F, Feilding A, Nutt DJ, et al. · eLife

Largest pre-registered self-blinding study of psychedelic microdosing to date. 191 participants who were already planning to microdose were randomized to placebo, microdose, or alternating-dose protocols using opaque capsules they prepared themselves. Mood and cognitive outcomes were measured at 4 weeks. Participants who believed they had microdosed reported substantial improvements regardless of what was actually in the capsule; no significant differences were found between actual microdose and placebo arms. The findings suggest much of the previously-reported microdosing benefits may be placebo-mediated.

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Wasser SP · Biomedical Journal

Broad review of the medicinal mushroom literature covering Ganoderma, Hericium, Lentinula, Trametes, Inonotus, Cordyceps, Grifola, and Pleurotus. Emphasizes the variability in commercial-product quality due to inconsistent fruit-body-vs-mycelium labeling and grain-substrate dilution. Reviews the published evidence for clinical applications, with strongest support for adjuvant cancer use of Lentinula lentinan and Trametes PSP/PSK fractions in Asian oncology practice.

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Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, et al. · New England Journal of Medicine

Phase II randomized double-blind controlled trial comparing two doses of psilocybin (25 mg × 2) plus 6 weeks of psychotherapy versus 6 weeks of escitalopram (10 mg/day, increased to 20 mg/day if tolerated) plus matched placebo psilocybin and matched psychotherapy in 59 patients with moderate-to-severe major depressive disorder. The primary outcome (QIDS-SR-16 change) showed numerical advantage for psilocybin but did not reach statistical significance under the pre-specified analysis. Secondary outcomes favored psilocybin. Both arms showed clinically meaningful improvement.

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Bolognini D, Rock EM, Cluny NL, Cascio MG, Limebeer CL, et al. · British Journal of Pharmacology

CBDA, the acidic precursor of CBD, was investigated in preclinical models of vomiting (Suncus murinus) and nausea-induced conditioned gaping (rats). CBDA was substantially more potent than CBD on a per-mg basis at suppressing both phenomena, mediated through enhanced 5-HT1A receptor activation. The findings are consistent with growing evidence that CBDA has its own pharmacology distinct from its decarboxylated form CBD, particularly at serotonergic targets.

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Huestis MA · Chemistry & Biodiversity

Comprehensive review of human pharmacokinetics for THC and metabolites across inhalation, oral, sublingual, and intravenous routes. Documents first-pass hepatic metabolism converting THC to 11-hydroxy-THC (~2-3× the CB1 affinity of parent THC), variable oral bioavailability (6-19%), and the dose-stacking risk inherent to oral cannabis. Reviews CBD pharmacokinetics including the inverted-U dose-response in some clinical contexts.

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Saitsu Y, Nishide A, Kikushima K, Shimizu K, Ohnuki K · Biomedical Research

Double-blind placebo-controlled trial in 31 healthy Japanese adults aged 50-80 receiving 3.2 g/day of lion's mane fruit body powder for 12 weeks. Cognitive endpoints (working memory, visuospatial reasoning) showed measurable improvement vs placebo over the dosing period. The dose used here is approximately 4× the dose in Mori 2009 and confirms the cognitive signal in a non-MCI population, though the sample size remains modest.

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Borrelli F, Fasolino I, Romano B, Capasso R, Maiello F, et al. · Biochemical Pharmacology

Investigated CBG in mouse models of colitis. CBG reduced inflammation markers (myeloperoxidase activity, iNOS expression, IL-1β/IFN-γ release) at doses of 1-30 mg/kg ip. Mechanism appears to involve CB2 receptor activation and α2-adrenoceptor agonism. CBG is one of the more-studied minor cannabinoids; clinical-trial evidence in humans remains thin.

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