Post Market Quality and Safety Surveillance of Commercial CBD Products: Composition and Drug to Drug Interaction Potential

Cannabidiol (CBD) is a non‑psychoactive phytocannabinoid that has gained considerable popularity for its therapeutic effects in epilepsy, anxiety and chronic pain ^1–3. In Zimbabwe, the Medicines Control Authority of Zimbabwe (MCAZ) authorized hemp‑derived CBD products as complementary medicines in July 2022, thereby creating a legal pathway for domestic sale ⁴. Registration requires manufacturers to submit a dossier that includes product samples, certificates of analysis and evidence of Good Manufacturing Practice compliance. However, post‑market surveillance (PMS) has not yet been implemented. Personal communication with an MCAZ official confirmed that the Authority has never performed PMS on a registered CBD product and does not require manufacturers to submit post‑market quality data.

Two safety concerns are particularly relevant in this context. Firstly, CBD is susceptible to oxidative degradation in oil matrices, a process that follows first‑order kinetics and is strongly temperature‑dependent, as described by the Arrhenius equation ^5–7. The warm climates of Harare and Bulawayo in Zimbabwe where summer peak temperatures can exceed 30˚C, may accelerate cannabinoid loss well beyond the rate anticipated by manufacturers. Secondly, CBD is a potent inhibitor of several UDP‑glucuronosyltransferase (UGT) enzymes, notably UGT1A9 and UGT2B7, which metabolize many commonly prescribed drugs ⁸. Co‑administration of CBD with UGT substrates can elevate plasma concentrations of the victim drug, potentially causing toxicity. Importantly, the first‑line antiretroviral dolutegravir is metabolized primarily by UGT1A1, an isoform that the parent CBD molecule does not strongly inhibit ^{9, 10}, suggesting a possible differential risk between modern and older HIV regimens.

The present study aimed to (i) project the stability of registered CBD products under Zimbabwean storage conditions using Arrhenius‑based kinetic modelling, (ii) predict the magnitude of UGT‑mediated DDIs for six commonly prescribed medications using a static mechanistic model and (iii) integrate the findings within the regulatory reality of absent PMS to inform evidence‑based recommendations.

2. MATERIALS AND METHODS

2.1 Product Identification and Labelled Concentrations

All MCAZ‑registered CBD complementary medicine products available in Harare and Bulawayo pharmacies were identified. A total of six products were found: one rectal suppository and five oral tinctures, two of which were formulated with full‑spectrum CBD distillate and three with CBD isolate. Labelled CBD and THC concentrations were recorded directly from the product packaging and used as initial (t = 0) values for all projections. Products were anonymised and assigned identifiers REC01 to REC06.

2.2 Environmental Data

Long‑term mean monthly temperature data for Harare and Bulawayo were obtained from the Zimbabwe Meteorological Services Department. Three storage scenarios were defined for each city: winter low (mean coolest month), mean annual and summer peak (mean warmest month). Temperatures used were: Harare; 12.1 ˚C, 18.5˚C, 28.2˚C; Bulawayo; 11.4 ˚C, 19.8˚C, 30.5 ˚C.

2.3 Degradation Kinetic Model

First‑order degradation rate constants for CBD were calculated for each temperature scenario using the Arrhenius equation in its two‑temperature form:

Where R is the universal gas constant (0.008314 kJ/mol·K). When the rate constant at a reference temperature Tref is known, the rate constant at a different temperature T was calculated by employing the above equation

The reference rate constant k_₂₅ = 4.2 × 10^⁻⁴ day^⁻¹ and activation energy Ea = 52.8 kJ mol^⁻¹ were taken from Kosović, et al. (2021) for CBD in sunflower oil ⁵, the matrix most similar to the carrier oils used in the registered products. For the suppository (REC01), a zero‑order model was applied.

Projected CBD concentrations were calculated at 6, 12, 18 and 24 months using the first‑order equation:

All products were assessed against a 90 % label‑claim threshold, consistent with pharmacopoeia specifications for content uniformity in herbal medicinal products ¹¹

2.4 THC Projections

For full‑spectrum products, the net THC concentration was modelled as the sum of two simultaneous first‑order processes: oxidative degradation of existing THC and formation of new THC via decarboxylation of residual tetrahydrocannabinolic acid (THCA):

  C_{thc,t=Cthc,0 x e-kthc.t+(Cthca,0 x (1-e-kdecarb.t))}

Kinetic parameters for THC degradation (k_₂₅ ≈ 3.0 × 10^⁻⁴day^⁻¹, Ea = 48.7 kJ mol^⁻¹) and THCA decarboxylation (k_₂₅≈ 1.2 × 10^⁻⁵ day^⁻¹, Ea = 88.2 kJ mol^⁻¹) were obtained from Meija, et al. (2021) ⁶ and Wang, et al. (2016) ⁷. Initial THCA content was conservatively assumed as 0.1 % of the labelled CBD content for full‑spectrum products and negligible for isolates.

2.5 Static Mechanistic DDI Model

A static mechanistic model, as recommended by the FDA ¹² and EMA ¹³ for early‑stage DDI screening, was applied to six victim drugs: dapagliflozin, dolutegravir, zidovudine, morphine, valproic acid and lorazepam. The predicted area‑under‑the‑curve (AUC) ratio was calculated as:

AUC Ratio= 1fm1+IKi+(1-fm)

Where fm is the fraction of the victim drug cleared by the inhibited UGT isoform, [I] is the unbound CBD concentration at the enzyme site and k_i is the inhibition constant.

Three CBD exposure scenarios were used, corresponding to the unbound inhibitor concentrations [I] = 0.013 μM (low, ~50 mg/day), 0.076 μM (moderate, ~300 mg/day) and 0.352 μM (high, Epidiolex®‑equivalent, 700 mg twice daily), derived from published pharmacokinetic data ¹⁴. Inhibition constants k_ᵢ for UGT1A9 (0.00075 μM) and UGT2B7 (0.0055 μM) were taken from Bansal, et al. (2025) ⁸. For dolutegravir, a conservative k_ᵢ of 10 μM was assumed for UGT1A1, justified by the absence of potent inhibition in published screening data.

Sensitivity analyses were performed by varying fm by ±20 % and k_ᵢ by ±50 %.

2.6 Mapping of Zimbabwean CBD Concentrations to DDI Benchmarks

To determine which exposure scenario is most clinically relevant for Zimbabwean patients, the projected CBD concentrations from the stability assessment were used to estimate the daily ingested dose for a typical consumption volume (3 mL) and the corresponding [I] value. These were then mapped onto the three DDI benchmarks.

3. RESULTS

3.1 Product Inventory and Labelled Content

The six registered products are described in Table 1. Labelled CBD concentrations ranged from 20 to 100 mg/mL for tinctures and 50 mg per unit for the suppository. All products stated THC < 0.1 %. Three products were CBD isolate formulations and two were full‑spectrum distillates.

DISCUSSION

This study is the first to project the stability of registered CBD products in Zimbabwe and to quantify UGT‑mediated DDI risks for drugs selected from the national formulary. The finding that all six products are projected to fall below the 90 % label‑claim threshold within 6–12 months under realistic storage conditions is consistent with experimental stability data from other laboratories ^5,6,15. The manufacturers’ own storage instruction “store below 30 °C” is already exceeded by Bulawayo summer peak temperatures, highlighting a gap between required storage and practical reality.

The DDI predictions extend the work of Bansal, et al. ⁸ by applying the static model to three additional drugs (lorazepam, morphine, valproic acid) and by including dolutegravir, the current first‑line antiretroviral in Zimbabwe. The finding that dolutegravir carries a negligible risk of parent‑mediated UGT interaction, while zidovudine shows a moderate interaction, provides a clinically actionable distinction. Patients on dolutegravir‑based regimens can be reassured, whereas those on zidovudine‑containing regimens require heightened vigilance if using CBD. The caveat that the CBD metabolite 7‑COOH‑CBD inhibits UGT1A1 in vitro ¹⁶ remains an important area for future research.

The integration of stability and DDI findings leads to the concept of a “shelf life–risk continuum”: a patient’s DDI risk is not static but shifts as the product ages and the real CBD dose changes. This dynamic risk is currently unmonitored because MCAZ lacks a PMS programme for complementary medicines. International best practice, as exemplified by the Therapeutic Goods Administration (Australia), the Health Sciences Authority (Singapore), Health Canada, and the Medicines and Healthcare products Regulatory Agency (UK), includes mandatory post‑market sampling, adverse event reporting and the power to recall non‑compliant products ^17–19. Within Africa, South Africa’s SAHPRA has conducted market surveys that revealed widespread label inaccuracy and THC contamination ²⁰, demonstrating the feasibility of such programmes in the region. The World Health Organization’s guidelines on safety monitoring of herbal medicines provide a normative framework that Zimbabwe has not yet adopted ^21-23.

CONCLUSION

Registered CBD products in Zimbabwe are vulnerable to significant degradation within a realistic shelf life, and clinically meaningful UGT‑mediated drug‑drug interactions with commonly prescribed medications are predicted at achievable CBD exposures. In the absence of post‑market surveillance, these risks are not detected or managed by the regulatory system. This study provides the scientific evidence to support the urgent establishment of a risk‑based PMS programme for CBD products in Zimbabwe, aligned with international standards, to safeguard public health.

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