Plant-derived compounds show potential for substance use disorders, depression, anxiety

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Frontiers in Medicine Published June 2, 2026 Medically reviewed June 2, 2026 DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Interpret these plant-derived compounds as investigational; evidence is preliminary with noted limitations.

This narrative review synthesizes mechanistic insights from structural biology and molecular pharmacology regarding plant-derived metabolites and essential oil preparations from Hypericum perforatum L., Rhodiola rosea L., Withania somnifera, and some essential oils. The authors discuss potential applications for substance use disorders, depression, and anxiety, drawing on preclinical and clinical evidence.

Key findings are qualitative, as no pooled effect sizes are reported. The review emphasizes that these natural compounds may offer therapeutic benefits, but the evidence is preliminary and requires further validation. The authors note several limitations including delayed onset of action, side effects, modest efficacy against emotional and cognitive symptoms, and challenges in bioavailability, standardization, and clinical validation.

No specific study population, sample size, comparator, or adverse event rates are reported. The review does not provide practice recommendations, and the authors caution that effects require further validation before clinical application. Clinicians should interpret these findings as exploratory and not yet ready for routine use.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedJun 2026

View Original Abstract ↓

Substance use disorders (SUDs) pose a major global health burden, often worsened by comorbid depression and anxiety. Dysregulation of monoaminergic neurotransmission, especially dopamine, serotonin, and norepinephrine transporters, underlies the reinforcing and harmful effects of addictive drugs. Current pharmacotherapies targeting these transporters offer benefits but are limited by delayed onset, side effects, and modest efficacy against emotional and cognitive symptoms. Despite advances in structural biology, a unified framework integrating transporter structure with docking and molecular dynamics simulations remains lacking. Emerging evidence suggests that plant-derived metabolites and essential oil preparations may modulate monoamine transporters through both direct and indirect mechanisms. These includes allosteric effects, membrane interactions, ion channel modulation, and downstream signaling pathways; however, these effects require further validation. This review summarizes recent preclinical and clinical data on transporter-modulating metabolites from Hypericum perforatum L., Rhodiola rosea L., Withania somnifera, and some of the essential oils. It highlights mechanistic insights from structural biology and molecular pharmacology, suggesting that plant-derived metabolites and essential oil preparations may influence monoaminergic neurotransmission and stress-related pathways. Despite challenges in bioavailability, standardization, and clinical validation, these metabolites may offer polypharmacology for adjunctive, personalized SUDs interventions. Integrated approaches, merging structural modeling, enhanced delivery, and rigorous trials, are needed.