Harnessing Cannabis sativa as a dual-use platform for biohydrogen production and pharmaceutical synthesis: a hypothesis and theory

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“Cannabis sativa, long established as a cornerstone of the pharmaceutical and industrial fiber markets, represents a radical and underexplored platform for renewable energy innovation.

In this Hypothesis and Theory framework, we introduce a novel, patented (Provisional Patent No. 63916615) dual-use bio-refinery paradigm. This model harnesses engineered cannabis photosynthesis to drive green hydrogen production without compromising its established value as a high-yield medicinal crop.

By strategically redirecting photosynthetic electron flow toward oxygen-protected hydrogenase activity, it is possible to generate molecular hydrogen at commercially relevant scales while maintaining plant viability.

Unique to this model is the ability to leverage over $10 billion in existing controlled-environment agriculture (CEA) infrastructure, bypassing the capital-intensive barriers that have hindered traditional algal biohydrogen systems. We outline a tripartite circular economy strategy that integrates hydrogen capture during the vegetative phase with the subsequent harvest of therapeutic cannabinoids and industrial biomass.

This convergence of synthetic biology, clean energy, and biomedicine positions cannabis as a uniquely versatile multipurpose crop capable of fueling both the pharmaceutical industry and the global transition to a sustainable hydrogen economy.”

https://pubmed.ncbi.nlm.nih.gov/42245109

“The global transition toward a net-zero carbon economy necessitates the development of scalable, carbon-negative energy sources. While hydrogen (H2) is a premier clean energy carrier, biological production methods have traditionally struggled with economic viability due to low feedstock density and high infrastructure costs. We propose that Cannabis sativa, a crop already optimized for high-density biomass and metabolic output, serves as the ideal biological “factory” to overcome these hurdles.”

“Cannabis sativa stands at the intersection of the most disruptive shifts in modern industry: the legalization of medicinal biotechnologies and the urgent need for carbon-negative energy transition.

By adopting this patented dual-use framework, we can transform one of the world’s most valuable crops into an engine for a sustainable, hydrogen-powered future.”

“Collaborative frameworks between synthetic biologists, agricultural engineers, and regulatory bodies will be essential to advance this platform toward commercial viability.”

https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2026.1833491/full

The Use of Cannabis sativa L. for Pest Control: From the Ethnobotanical Knowledge to a Systematic Review of Experimental Studies

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“Background: Despite the benefits that synthetic pesticides have provided in terms of pest and disease control, they cause serious long-term consequences for both the environment and living organisms. Interest in eco-friendly products has subsequently increased in recent years. 

Methods: This article briefly analyzes the available ethnobotanical evidence regarding the use of Cannabis sativa as a pesticide and offers a systematic review of experimental studies. 

Results: Our findings indicate that both ethnobotanical and experimental procedures support the use of C. sativa as a pesticide, as remarkable toxicity has been observed against pest organisms. The results included in the systematic review of experimental studies (n=30) show a high degree of heterogeneity, but certain conclusions can be extracted to guide further research. For instance, promising pesticide properties were reported for most of the groups of species tested, especially Arachnida and Insecta; the efficacy of C. sativa as a pesticide can be derived from a wide variety of compounds that it contains and possible synergistic effects; it is crucial to standardize the phytochemical profile of C. sativa plants used as well as to obtain easily reproducible results; appropriate extraction methods should be explored; and upper inflorescences of the plant may be preferred for the production of the essential oil, but further studies should explore better other parts of the plant. 

Conclusion: In the coming years, as new findings are produced, the promising potential of C. sativa as a pesticide will be elucidated, and reviews such as the present one constitute useful basic tools to make these processes easier.”

https://pubmed.ncbi.nlm.nih.gov/34612729

https://journals.sagepub.com/doi/10.1089/can.2021.0095

The potential of Allium sativum and Cannabis sativa extracts for anti-tick activities against Rhipicephalus (Boophilus) microplus

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“The efficacy of Allium sativum and Cannabis sativa against Rhipicephalus microplus ticks was evaluated using the adult immersion and the larval packet test. In addition, an in silico approach was utilized by performing a docking study in order to identify the active ingredients from both plants.

Results showed a comparatively high lethal effect of A. sativum and C. sativa on egg laying (index of egg laying = 0.26 and 0.24, respectively), egg hatching (33.5 and 37.1, respectively), and total larval mortality (100%, both), at 40 mg/mL.

When applied to cattle which had been inoculated with larvae ticks, it was observed that a 45% solution of both herbal extracts significantly reduced the number of ticks by 96 h post treatment.

We analyzed in silico 27 known active molecules from both plants and identified in the PubChem database to explore the hypothesis that the effect found on ticks was based on inhibition of acetylcholinesterase (AChE).

Vitamin E and cannabidiol are the most potent AChE inhibitors with docking scores of -15.85 and -14.38, respectively.

Based on these findings, we conclude that A. sativum and C. sativa may potentially be used for the control of R. microplus, and should be further investigated as a potential supplement to or replacement of synthetic acaricides.”

https://pubmed.ncbi.nlm.nih.gov/32886258

https://link.springer.com/article/10.1007/s10493-020-00540-z

Cannabidiol-thiosemicarbazone exhibits dual tyrosinase inhibition and antioxidant activity in human skin-derived cells

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“The search for modulators of melanogenesis with improved biological compatibility remains an active area of investigation, as existing tyrosinase (TYR) inhibitors are often limited by low potency, instability, or cytotoxicity.

Here, we investigated CBD-TSC1, a cannabidiol-based thiosemicarbazone derivative, as a TYR-targeting scaffold.

Structural characterization confirmed a single, stable E-isomer, and pKa profiling together with kinetic analyses indicated reversible mixed-type inhibition of human TYR, involving interactions with both free enzyme and enzyme-substrate complexes. CBD-TSC1 exhibited higher inhibitory activity than CBD and kojic acid under the tested conditions while maintaining low cytotoxicity in G361 melanoma and HaCaT keratinocyte cell lines. In addition, CBD-TSC1 reduced intracellular oxidative stress at low micromolar concentrations. In zebrafish larvae, treatment with CBD-TSC1 resulted in a dose-dependent reduction in melanin content, comparable to that of kojic acid under identical experimental conditions, supporting an association between thiosemicarbazone modification and the observed biological activity.

Overall, CBD-TSC1 demonstrated consistent activity across biochemical, cellular, and zebrafish-based assays under the tested conditions. Although the mechanistic relationship between TYR inhibition, redox modulation, and melanogenesis regulation remains to be fully clarified, the present findings support further investigation of cannabidiol-based thiosemicarbazone derivatives as modulators of TYR-related pathways.”

https://pubmed.ncbi.nlm.nih.gov/42235859

“CBD-TSC1 is a novel cannabidiol-thiosemicarbazone hybrid with dual anti-melanogenic activity.”

“Thiosemicarbazone modification is essential for superior enzymatic and redox performance.”

https://www.sciencedirect.com/science/article/abs/pii/S0960894X26001745?via%3Dihub

Cannabidiol attenuates tau hyperphosphorylation and cognitive deficits in an experimental model of Alzheimer’s disease and is associated with restoration of PP2A expression

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“Pathogenic tau hyperphosphorylation, together with reduced protein phosphatase 2 A (PP2A) expression, is associated with neurofibrillary tangle formation and cognitive deterioration in Alzheimer’s disease (AD).

Cannabidiol (CBD), a non-psychotropic phytocannabinoid, remains insufficiently studied for its potential to modulate the PP2A-tau axis in experimental AD.

This study evaluated whether CBD improves hippocampus-dependent spatial cognition in a D-galactose/AlCl₃ rat model of AD and whether these effects are associated with restoration of PP2A expression and attenuation of tau hyperphosphorylation.

AD-like pathology was induced in male Wistar rats by D-galactose (60 mg/kg i.p.) and AlCl₃ (200 mg/kg oral gavage) for 10 weeks, followed by CBD (20, 40 or 80 mg/kg) or donepezil (1 mg/kg) for three weeks. The Morris water maze, Jess Simple Western, and ELISA were used to assess cognition, PP2A expression, and p-tau levels, respectively.

CBD significantly improved spatial learning and memory. PP2A expression increased across all tested doses, with the highest mean level observed at 80 mg/kg. Hippocampal p-tau levels were significantly increased in the model group and significantly reduced by all CBD doses and donepezil (all p < 0.0001 vs. model). The inverse relationship between PP2A expression and p-tau levels suggests possible involvement of the PP2A-tau axis.

CBD attenuated cognitive deficits and tau hyperphosphorylation alongside restoration of PP2A expression, suggesting that the PP2A-tau axis may be a relevant therapeutic target in AD-related tauopathy.”

https://pubmed.ncbi.nlm.nih.gov/42240860

https://link.springer.com/article/10.1007/s11011-026-01894-w

Interplay between the HPA axis and inflammation as mechanisms therapeutic targets of Cannabis sativa in depression

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“Major Depressive Disorder (MDD) is a highly prevalent and disabling psychiatric disorder, representing a major global health burden across all age groups.

Increasing evidence indicates that its pathophysiology involves a complex interplay between chronic stress, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, immune activation, and neuroinflammation. Persistent HPA axis hyperactivity, glucocorticoid resistance, and altered expression of key regulators such as FKBP51 contribute to sustained inflammatory signaling and impaired neural plasticity in brain regions involved in mood regulation. Epigenetic mechanisms, including DNA methylation and microRNA-mediated regulation, further modulate stress responsivity, inflammatory pathways, and vulnerability to major depressive disorder.

In this context, growing attention has been directed toward Cannabis sativa and its bioactive constituents as potential therapeutic agents.

Preclinical and clinical evidence suggest that cannabinoids may modulate the endocannabinoid system, attenuate HPA axis hyperactivity, reduce neuroinflammation, and influence monoaminergic and neuroplasticity-related pathways.

This review synthesizes the current literature on the mechanistic links among the HPA axis, inflammation, and MDD, highlighting the emerging role of Cannabis sativa-derived compounds in targeting these interconnected pathways.”

https://pubmed.ncbi.nlm.nih.gov/42239513

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1801474/full

Cannabis for tic control: a systematic review and meta-analysis of its efficacy in Tourette syndrome management

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“Background: Tourette syndrome (TS) involves motor and vocal tics, often with obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). Cannabis-based medicines (CBMs) are a potential therapy due to their interaction with the endocannabinoid system, potentially reducing tics and associated symptoms. Compared to antipsychotics, CBMs may offer improved tolerability and fewer side effects. Although evidence is limited, emerging studies suggest their potential to improve quality of life in TS. This review was registered with PROSPERO (CRD420251088633).

Aim: To evaluate the effectiveness of CBMs in treating TS.

Methods: We systematically searched PubMed, Google Scholar, ScienceDirect, and the Cochrane Collaboration Database for cohort studies and randomized controlled trials (RCTs) up to July 2, 2025. Data extraction included study characteristics and efficacy outcomes measured by the Yale Global Tic Severity Scale (YGTSS) and Premonitory Urge for Tics Scale (PUTS). Meta-analysis using Review Manager 5.4 compared pre- and post-treatment scores using mean difference (MD) and 95% confidence intervals (CI).

Results: From 1,105 screened articles, eight studies met inclusion criteria for the review, and seven were included in the meta-analysis, involving 306 adult TS patients. CBMs significantly reduced YGTSS scores (MD = – 13.29, 95% CI [-21.67 to – 4.91], P = 0.002) and PUTS scores (MD = – 4.09, 95% CI [-7.24 to – 0.93], P = 0.01).

Conclusion: CBMs show promising potential in reducing tics and premonitory urges in TS. Larger, placebo-controlled trials are needed to confirm efficacy, ensure safety, and optimize dosing.”

https://pubmed.ncbi.nlm.nih.gov/42229830

“Cannabis-based medicines significantly reduced tic severity in Tourette syndrome.”

https://www.ibroneuroscience.org/article/S0306-4522(26)00367-2/abstract

Structural characterization and in vitro evaluation of the hypolipidemic activity of the HSP-Ia, a bioactive polysaccharide derived from hemp (Cannabis sativa L.) seeds

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“A novel polysaccharide, HSP-Ia, with a molecular weight of 973.6 kDa, was isolated from hemp (Cannabis sativa L.) seed residues using sequential aqueous extraction, ethanol-induced precipitation, and chromatographic fractionation.

Its structural attributes were determined through methylation profiling and nuclear magnetic resonance spectroscopy. The physicochemical characteristics were examined using X-ray diffraction, atomic force microscopy, scanning electron microscopy, and circular dichroism spectroscopy. The hypolipidemic potential of HSP-Ia was assessed using oxidized low-density lipoprotein-induced RAW264.7 macrophages.

HSP-Ia was predominantly comprised of glucose, with minor proportions of arabinose and galactose. It had a backbone of →6)-α-D-Glcp-(1 → residues with side chains attached at the O-2 and O-3 positions. HSP-Ia possessed an amorphous, nonuniform, and discontinuous morphology, with height distributions ranging from 0.7 to 10.5 nm. It exhibited a zeta potential of -7.4 mV and retained a triple-helix conformation in aqueous media. Notably, HSP-Ia facilitated lipid efflux in foam cells in a dose-dependent manner, associated with the upregulation of Liver X receptor α/ATP-binding cassette transporter signaling pathway.

Overall, these findings enhance the current knowledge of the structural features of hemp seed-derived polysaccharides and underscore the potential application of HSP-Ia as a lipid-modulating agent in the development of functional food products and pharmaceutical formulations.”

https://pubmed.ncbi.nlm.nih.gov/42230038

“Hemp seed, the mature dried seed of Cannabis sativa L., is a prominent traditional medicinal and dietary crop in China, recognized as one of the “Dragon Nine Flavours” and often termed “longevity hemp”. According to traditional Chinese medicine theory, hemp seed is associated with the meridians of the spleen, stomach, and large intestine and is used to lubricate the intestines, alleviate constipation, tonify deficiency, and enhance circulation. Hemp seed is rich in proteins, lipids, vitamins, and carbohydrates and has extensive applications in the food and livestock feed sectors. Contemporary studies support these traditional uses, demonstrating that regular consumption of hemp seed can improve gastrointestinal function and reduce the risk of chronic diseases.”

“This study successfully isolated and characterized a novel polysaccharide, designated HSP-Ia, from hemp (C. sativa L.) seed residues.”

https://www.sciencedirect.com/science/article/abs/pii/S0144861726005564?via%3Dihub

UK Medical Cannabis Registry: an updated analysis of clinical outcomes of medicinal cannabis therapy for hypermobility-associated chronic pain

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“Introduction/objective: The primary aim of this study was to evaluate changes in pain-specific and general health-related quality of life in individuals prescribed cannabis-based medicinal products (CBMPs) for hypermobility-associated chronic pain.

Methods: The case series utilised data from the UK Medical Cannabis Registry. Primary outcomes were changes in Brief Pain Inventory (BPI), Pain Visual Analogue Scale (VAS), Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2), EQ-5D-5L index value, Generalised Anxiety Disorder-7 (GAD-7), and Single-item Sleep Quality Scale (SQS) over 24 months. Repeated measures analysis of variance was used to assess changes over time, with post hoc pairwise comparisons performed for significant findings.

Results: A total of 240 patients were analysed. Changes were observed across all patient-reported outcome measures (PROMs) on repeated measures analysis of variance (p < 0.001). Post hoc pairwise comparisons for the BPI subscales, SF-MPQ-2 and Pain VAS demonstrated improvement from baseline to all subsequent timepoints (p < 0.001). By 24 months, 56.67% (n = 136) and 61.25% (n = 147) of participants reported clinically significant improvements in BPI severity and interference respectively. Clinically significant improvements were also reported for SF-MPQ-2 (47.08%, n = 113) and Pain VAS scores (60.00%, n = 144).

Conclusion: In this real-world cohort, CBMP treatment was associated with sustained improvements in outcomes for individuals with hypermobility-associated chronic pain. These findings support the need for further controlled studies to determine causality.

Key Points • This 24-month real-world study demonstrates sustained improvements in pain, anxiety, and sleep outcomes for patients with hypermobility-associated chronic pain treated with cannabis-based medicinal products, with approximately 60% achieving clinically meaningful pain reductions.

• Cannabis-based medicinal products were associated with reductions in concomitant opioid prescriptions at 12, 18, and 24 months.

• This represents the largest and longest-duration observational study of medical cannabis therapy specifically in hypermobility spectrum disorders and Ehlers-Danlos syndrome, addressing a critical evidence gap in chronic pain management.

• Adverse events were predominantly mild-to-moderate in severity, with poor baseline sleep quality and current cannabis use identified as positive predictors of pain improvement, informing patient selection and treatment optimisation.”

https://pubmed.ncbi.nlm.nih.gov/42217098

“This study provides a 24-month real-world evaluation of CBMPs in patients with hypermobility-associated chronic pain. It demonstrates long-term sustained improvement in pain, anxiety and sleep-related outcomes, underpinning health-related quality of life. Despite its observational design, the study provides important insight into potentially addressing an area of significantly unmet therapeutic need.”

https://link.springer.com/article/10.1007/s10067-026-08166-z

Selective opioid-sparing effects of cannabidiol on opioid analgesia in rats

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“Cannabidiol, a major non-psychoactive constituent of cannabis, has generated interest as a novel therapeutic for managing several pathological conditions including chronic pain and opioid use disorder.

Here, we evaluated the effects of cannabidiol (3.2 or 10.0 mg/kg) on the antinociceptive and the reward-related effects of the opioid analgesic oxycodone (0.56 mg/kg) in rats (male and female Sprague-Dawley) using an operant facial pain assay, locomotor activity monitoring, and the conditioned place preference paradigm.

Cannabidiol enhanced the antinociceptive effect of oxycodone without affecting oxycodone-induced rearing behavior, or the acquisition and expression of oxycodone conditioned place preference under the conditions tested.

Together, these findings suggest that cannabidiol potentiates the analgesic effects of oxycodone without affecting its reward-related properties. These results support the potential of cannabidiol as an adjunctive, opioid-sparing agent in pain management.

PERSPECTIVE: Opioids remain important for treating moderate to severe pain, but adverse effects and misuse liability limit their use. These preclinical findings suggest cannabidiol may enhance oxycodone antinociception under acute painful conditions, without increasing abuse-relevant effects under the conditions tested, supporting further study as an opioid-sparing adjunct.”

https://pubmed.ncbi.nlm.nih.gov/42219047

https://www.jpain.org/article/S1526-5900(26)00156-2/abstract