Phytocannabinoid suppository support. The formulation rationale, the evidence base, the delivered doses and the indications for each of the two formulations, in one reference.
This is a two formulation phytocannabinoid suppository line built on a single design principle: a broad spectrum cannabinoid base, boosted with targeted single cannabinoid isolates to raise the clinically relevant minors to doses where their documented target engagement becomes meaningful.
That combination is uncommon. The greater part of the hemp market sells single molecule products, almost always CBD, which discard the rest of the plant and are limited by a narrow effective window. The remainder sell whole plant preparations at whatever ratios the plant happened to provide, where the therapeutically interesting minors sit too low to do useful work. This line takes the evidence-backed advantages of the whole plant matrix and then corrects its main weakness.
Foundation, 130 mg. The entry formulation for general endocannabinoid system regulation, wellness across the lifespan, sensitive populations, women's health, and as a defined reset course for patients without active disease.
Advanced Care, 400 mg. The therapeutic formulation for active and advanced disease, covering autoimmune conditions, oncology adjunct at all stages, chronic inflammatory disease, neurodegenerative disease and palliative care.
One blend at two strengths. Both formulations carry the same cannabinoid ratios throughout, and Advanced Care carries roughly three times the load of Foundation. Because the profile is identical, a patient stepping up receives more of the same preparation rather than a different one, which simplifies titration and makes tolerance at Foundation a reliable predictor of tolerance at Advanced Care.
Almost all of the published human dosing evidence for cannabinoids has two features that must be stated plainly at the outset, because they define both what the literature supports and what it does not describe. First, the strong evidence is for cannabidiol as a single isolated molecule. Second, it is almost entirely an oral evidence base. The representative oral single molecule CBD doses are recorded below for completeness.
| Use context, single molecule CBD, oral | Representative daily CBD |
|---|---|
| General use and chronic pain | approximately 25 to 150 mg per day8 |
| Acute anxiety, single doses | approximately 300 to 600 mg16 |
| Parkinson's disease, exploratory trial | 300 mg per day28 |
| Refractory epilepsy, approved oral solution | 10 to 20 mg per kg per day, about 700 to 1,400 mg at 70 kg |
| CBD-rich extract versus purified CBD, epilepsy | 6.0 versus 25.3 mg per kg per day3 |
This product is not a CBD product, and it is not oral. Each suppository delivers ten phytocannabinoids together. Six are raised by targeted isolate, CBD, CBG, CBN, CBDa, CBGa and CBC, and four more are carried by the broad spectrum base at their natural ratios, CBE, CBTC, CBDV and CBL. To read such a formulation through the lens of its CBD content alone, and to benchmark it against single molecule oral CBD dose bands, misrepresents what it is and what it is designed to do. The single molecule figures above are recorded as the boundary of the existing evidence, not as the measure of this line.
The relevant evidence is the evidence on whole, multi-cannabinoid preparations, and it points in a consistent direction: a cannabinoid matrix achieves its effect at substantially lower per-cannabinoid doses than purified CBD, roughly a quarter of the dose in the epilepsy meta-analysis, and without the bell-shaped ceiling that limits the isolate.2,3 The clinical weight of a suppository in this line comes not from any single cannabinoid reaching a high milligram figure, but from a combined load of 130 to 400 mg across ten cannabinoids engaging the inflammatory and immune targets, the oncological targets, and the neurodegenerative targets at once.
The endocannabinoid system is a signalling network that helps the body hold itself in balance. Where blood pressure, blood sugar and body temperature each have regulatory mechanisms that pull them back toward a set point, the endocannabinoid system performs a comparable balancing role across the nervous, immune, digestive and endocrine systems. It does not drive a single function so much as moderate many of them, damping signalling that has run too high and supporting it where it has fallen too low.5
It has three working parts. First, two principal receptors: CB1, concentrated in the brain and nervous system, and CB2, concentrated in immune and peripheral tissue. Second, the body's own signalling molecules that act on those receptors, the endocannabinoids anandamide and 2-AG. Third, the enzymes that build and break down those molecules, principally FAAH, which clears anandamide, and MAGL, which clears 2-AG. The resting activity of this network is often described as endocannabinoid tone.
Plant cannabinoids interact with this system in two ways. Some bind the receptors directly, as CBN does at CB1. Others act indirectly or at neighbouring targets, as CBD does by slowing the breakdown of anandamide and by acting at the TRPV1 ion channel, the 5-HT1A serotonin receptor, the PPAR-gamma nuclear receptor and GPR55. This is the key point for what follows: the cannabinoids in this line act not at one target but across a panel of them. A formulation that engages several of these at once is doing something different from a single molecule acting at a single site.
There are three broad ways to formulate a cannabinoid product. Each has a defensible place, and the differences between them are not marketing distinctions but measurable pharmacology.
Isolate only. A single purified cannabinoid, almost always CBD, with everything else removed. Precise and inexpensive, but limited by a bell-shaped dose-response that gives it a narrow effective window, by single target action, and by more frequent adverse effects at the doses required.
Unboosted whole plant extract. A full or broad spectrum extract used as it comes. This recovers the entourage effect and a clean dose-dependent response, but locks the formulator to whatever ratios the extract happens to contain, which are CBD-dominant and leave the therapeutically interesting minors too low to reach a meaningful dose.
A broad spectrum base with targeted isolate boosting, the approach of this line. The base supplies the matrix and its favourable dose-response, and individual isolates are then added to raise the clinically relevant cannabinoids to doses where their documented target engagement becomes meaningful. It asks considerably more of the formulator, including a correction against every incoming lot, and that is the trade it makes.
The limitation is not theoretical. In a controlled comparison, purified CBD given to mice produced a bell-shaped dose-response in anti-inflammatory and anti-pain testing, effective only in a narrow middle band and losing effect as the dose rose beyond it. A CBD-rich whole extract tested alongside it produced a clean dose-dependent response that kept improving. The authors attributed the difference to the other plant constituents working alongside CBD.2
The clinical signal points the same way. A meta-analysis of observational data in treatment-resistant epilepsy found that patients on CBD-rich extracts reached comparable responder rates to those on purified CBD at roughly a quarter of the dose, an average of 6.0 against 25.3 mg per kg per day, and with significantly fewer mild and severe adverse effects.3
The caveat a careful reader will want stated. At the strict threshold of a 50 per cent or greater seizure reduction the responder rates did not differ significantly between the two. The extract's advantage was in dose efficiency and tolerability rather than in raw ceiling efficacy, and the data is observational rather than randomised. The mechanistic basis proposed for these observations is the entourage effect, the synergy between cannabinoids and terpenes framed in the modern literature by Russo.4
The choice of base is not incidental, and it is the mechanism by which the rare minor cannabinoids enter the formulation at all rather than having to be bought and added one by one.
Ordinary CBD distillate is a problem for anyone formulating for breadth. Above roughly 60 per cent CBD it crystallises, the molecules stacking into a solid that ruins a batch. The standard industry response is to push the CBD purity higher still, which strips the minor cannabinoids out almost entirely. CBD isolate, at the far end of that same process, contains none at all.
A crystal resistant distillate is engineered for the opposite outcome, and the reason is elegant. The minor cannabinoids are precisely what interrupt crystallisation. Their differing molecular shapes prevent the CBD from packing into an ordered lattice, so the material stays liquid. It follows that a distillate formulated to stay liquid is by necessity a distillate that has retained a high minor cannabinoid fraction. The property that makes it workable and the property that makes it therapeutically interesting are the same property. Material of this type typically carries on the order of 15 to 25 per cent minor cannabinoids alongside its CBD, a far broader profile than ordinary distillate holds and a world apart from isolate.
The practical consequence is that the base supplies the rare minors as a natural, balanced fraction rather than as a stack of separately purchased single cannabinoid isolates. The targeted additions are then reserved for the specific cannabinoids the pharmacology singles out for elevation. That is the structural reason this line can claim genuine breadth alongside a controlled, repeatable composition, and it is an approach comparatively few formulators take.
The minor cannabinoids that the target analysis in the next section identifies as the interesting ones, CBG at cytochrome c, CBDa at TNF-alpha, CBN across the protein kinase and glutathione transferase panel, CBC at CB2 and TRPA1, sit in an unmodified extract at concentrations far too low for their documented engagement to mean anything at a sensible dose.
A patient taking such a preparation is, in practice, taking a CBD product with traces of everything else. The pharmacology that makes the whole plant argument compelling is present on the certificate and absent from the effect. Raising those cannabinoids by targeted addition is what closes that gap, and it is the reason this line can claim genuine multi-target coverage rather than merely genuine breadth.
A crystal resistant broad spectrum base is preferred over isolate because it carries the matrix that flattens the bell curve and lowers the effective dose, and because staying liquid is what proves it has kept its minors. Targeted isolates are then added because the base alone cannot deliver those minor cannabinoids at the doses the pharmacology calls for. That is the design the line is built on. The delivered figures are set out in the next section. The materials used, their assays, the quantities of each input and the method by which the profile is achieved remain proprietary to Bonner Biotech LLC.
The figures below are delivered doses, meaning the quantity of each cannabinoid that reaches the patient in a single suppository, combining what the crystal resistant base contributes with what the targeted isolates add. They are the figures a prescriber needs and the figures a certificate of analysis on the finished product will show. Every input is screened under ISO/IEC 17025 accreditation for pesticides, heavy metals and residual solvents, and total THC is not detected in the base material.
The crystal resistant broad spectrum base is naturally produced rather than synthesised or reconstructed, so its cannabinoid distribution is characteristic of the specific production lot and varies from one lot to the next. The isolate additions are near-pure single molecule inputs and do not vary.
Each formulation is dosed so that the total cannabinoid load per suppository stays constant across lots. What shifts is the internal balance of the base-derived fraction, and the isolate charge is corrected against every incoming lot to hold the delivered figures steady. Every production batch is assayed. Practitioners should request the certificate for any batch dispensed rather than relying on these figures indefinitely.
These are delivered figures, the quantity of each cannabinoid reaching the patient in one 2 mL suppository, verified by certificate of analysis on the finished product. The final line is the combined contribution of the minor cannabinoids carried by the base, described in section seven.
| Cannabinoid | Foundation | Advanced Care |
|---|---|---|
| CBD | 50.19 | 154.42 |
| CBG | 29.89 | 91.98 |
| CBN | 18.56 | 57.09 |
| CBDa | 9.97 | 30.64 |
| CBGa | 8.77 | 26.96 |
| CBC | 6.61 | 20.32 |
| Cannabinoids carried by the base, combined | 6.04 | 18.57 |
| Total delivered | 130.0 | 400.0 |
| Total THC, worst case | 0.019 | 0.057 |
Net delivered CBD of approximately 50 mg in Foundation and 154 mg in Advanced Care sits within and above the validated chronic pain therapeutic band of 25 to 150 mg per day for oral single molecule CBD.8 That band is a reference point for scale, not a claim of equivalence, since the route and the preparation both differ.
A 2022 network-based pharmacology study provides a systems-level characterisation of cannabinoid-protein interactions.1 Using molecular docking simulation against eighteen essential protein targets, the authors mapped eight key cannabinoids to four functional modules that together cover the major disease categories where cannabinoid therapy has documented or proposed utility. This line is anchored to that evidence base, with each cannabinoid selected for its measurable binding affinity to disease-relevant protein targets.
| Module | Disease pathways and protein targets | Ligands supplied by this line |
|---|---|---|
| One | Amyotrophic lateral sclerosis, hepatocellular carcinoma, prostate cancer and oxidative stress, through CAT, COMT, CYP17A1, GSTA2, GSTM3, GSTP1 and HMOX1 | CBD, CBDa, CBN, CBC |
| Two | The largest module. Huntington's, Parkinson's and Alzheimer's pathways, multiple cancer pathways, type 1 and 2 diabetes, and rheumatoid arthritis, through AKT1, CASP9, PLCG1, PRKCA and PRKCB | CBD, CBDa, CBN, CBC, CBGa |
| Three | Inflammatory bowel disease, ulcerative colitis and type 2 diabetes, through CYCS and TNF | CBG, CBD, CBDa |
| Four | Epilepsy, Alzheimer's, Parkinson's, Huntington's and ALS, through CNR1, CNR2, CREB1 and GRIN2B | CBC, CBD, CBDa, CBG, CBGa, CBN |
The source study also assigned Delta-8 and Delta-9-THC as ligands across Modules 3 and 4. Neither is present in this line, so the GRIN2B target within Module 4 is not engaged by any cannabinoid in these formulations. That gap is stated openly here because it was the pharmacological argument for the discontinued Neuro Complex.
Binding energy below minus 5.0 kcal per mol indicates strong binding in this analysis, and below minus 8.0 indicates very strong binding.
| Cannabinoid | Target | kcal/mol | Relevance |
|---|---|---|---|
| CBDa | TNF-alpha | -10.5 | Strongest TNF binder in the line |
| CBN | CNR1 (CB1) | -9.4 | Strongest CB1 binder tested |
| CBD | CNR2 (CB2) | -9.2 | Strong CB2 immunomodulation |
| CBD | AKT1 | -8.8 | Cell survival and growth factor signalling |
| CBDa | AKT1 | -8.8 | Cell survival and growth factor signalling |
| CBN | PRKCB | -8.5 | Cell cycle and cancer signalling |
| CBN | CNR2 (CB2) | -8.5 | Immune modulation |
No single cannabinoid covers all four functional modules. Coverage across them requires multiple ligands binding multiple targets, which is the principle on which this line is built.
Indirect endocannabinoid modulation via FAAH inhibition and allosteric CB1 modulation, with secondary action at TRPV1, 5-HT1A, PPAR and GPR55. Strong CB2 binding at minus 9.2 kcal per mol.
The highest degree centrality of any cannabinoid in the source analysis, engaging 126 protein targets across Modules 1, 2 and 4. Pro-apoptotic action mediated via CASP9.1
Base-derived CBD plus isolate brings delivered CBD to approximately 50 mg in Foundation and 154 mg in Advanced Care. Anti-inflammatory action via TNF-alpha and NF-kB pathways is reported in preclinical ischaemia work.18
Direct CB1 and CB2 partial agonism, alpha-2 adrenoceptor agonism, TRPA1 modulation and PPAR activation.
Essential binding partner for cytochrome c in Module 3, engaging CNR1 and CNR2. The CYCS engagement is mechanistically significant for the apoptotic pathway.
Anti-inflammatory activity in rheumatoid arthritis synovial fibroblasts is reported, mediated partly through TRPA1.19 A CBG quinone derivative shows PPAR-mediated neuroprotection in the 6-OHDA Parkinson's model.29 A 2024 controlled field trial reported acute anxiety and stress reduction.20
CB1 partial agonist and the strongest CB1 binder tested at minus 9.4 kcal per mol, CB2 active at minus 8.5, with TRPA1 activity, sedative and analgesic action, and appetite support relevant to cachexia.
The broadest single cannabinoid coverage in the line, binding CNR1, CNR2, PRKCB, PRKCA, GSTP1, COMT, HMOX1, GSTM3, GSTA2 and CREB1. The COMT binding is relevant to disrupted catecholamine metabolism in Parkinson's.
Sedation is one role but not the dominant one for chronic use. Held proportionally lower relative to CBD than in earlier formulations of this line.
Selective COX-2 inhibitor with roughly a hundred times the 5-HT1A affinity of CBD, with TRPV1 and TRPA1 modulation.17
The strongest TNF-alpha binder in the cannabinoid family at minus 10.5 kcal per mol, also binding AKT1, CAT, CYP17A1, CASP9, PRKCA, CNR1 and CNR2 across all four modules.
The strongest anti-inflammatory profile in the line. COX-2 downregulation in breast cancer cells is reported.21,22 Acidic cannabinoid pharmacology is reviewed in full elsewhere.23 Requires cool storage to limit decarboxylation.
COX-2 inhibition and PPAR agonism.
Essential binding partner for PLCG1 in Module 2, with CNR1 and CNR2 binding. PLCG1 engagement is linked to growth factor receptor and cancer signalling.
Complementary to CBG, contributing COX-2 and PPAR engagement. Raised by isolate, since the base carries no acidic cannabinoid at a useful level.
Selective CB2 agonist24 and the most potent phytocannabinoid activator of TRPA1, with an EC50 of 90 nM.25 Anandamide reuptake inhibition and documented neurogenic activity, one of the few cannabinoids with this property.26
Binds PRKCA, PRKCB, GSTP1, HMOX1, GSTM3, GSTA2, CNR1 and CNR2 across Modules 1, 2 and 4. The HMOX1 and glutathione transferase binding addresses oxidative stress pathways.
Anti-inflammatory activity in murine colitis is reported,27 along with cytotoxic activity in cell culture work.30
The four cannabinoids below are not separately boosted. They are present at the natural ratios of the base and therefore vary from lot to lot. They are not part of the network pharmacology docking dataset, so their contribution is best understood as part of the matrix rather than as a discretely dosed target. They are characterised honestly below, including where the published pharmacology is limited.
| Cannabinoid | What is known |
|---|---|
| Cannabidivarin, CBDV | The propyl homologue of CBD, non-psychoactive. Modulates and desensitises TRPV1, TRPA1 and TRPM8. An anticonvulsant signal is reported in preclinical seizure models and early phase human epilepsy work. |
| Cannabielsoin, CBE | A naturally occurring oxidative transformation product of CBD. Its pharmacology is not well characterised and no defined receptor target has been established. |
| Cannabicitran, CBTC | A minor cyclised cannabinoid with limited characterised pharmacology. No defined receptor activity has been established in the published literature. |
| Cannabicyclol, CBL | A photochemical conversion product of CBC formed naturally as an extract matures. No significant receptor activity has been characterised. |
The route and the base are a single design decision. Oral cannabinoids are absorbed poorly and erratically. CBD taken by mouth reaches systemic circulation at under ten per cent, often around six, because cannabinoids are intensely lipophilic, poorly soluble in the gut and heavily metabolised by the liver on first pass.6 The suppository in a lipid base is built to work around both problems at once.
The lower and middle rectal veins drain into the systemic circulation rather than through the portal vein and the liver, so a rectally delivered drug sidesteps much of the hepatic first-pass metabolism that limits oral dosing, and avoids the acidic, enzymatic environment of the stomach entirely. This is not a cannabis-specific quirk but an established route principle: for a range of drugs including morphine, metoclopramide, ergotamine, lidocaine and propranolol, rectal administration produces systemic exposure that exceeds the oral route.7,15
The more important mechanism, and the reason the base is a designed delivery system rather than a moulding medium, is lymphatic transport. Molecules with a partition coefficient above log P 5 and high solubility in long-chain triglyceride associate with chylomicrons, the lipid carriers assembled during fat absorption, and are carried into the lymphatic system and from there directly into the systemic circulation, bypassing the liver. CBD sits squarely in this range, with a log P of approximately 6.3.
Co-administration of cannabinoids with long-chain lipids has been shown to increase CBD and THC systemic exposure roughly threefold against a lipid-free preparation, with cannabinoid concentrations in the lymph reaching 100 to 250 times those in plasma.9,10 Oil composition matters to the effect, and long-chain vegetable oils outperform medium-chain ones.14
This reframes the fatty base. A lipophilic cannabinoid in a fatty vehicle releases slowly into the watery mucosal layer, the conventional absorption route, but that is not the route the formulation depends on. Cocoa butter is built from long-chain fatty acids, principally stearic, oleic and palmitic, and apricot kernel oil is largely oleic and linoleic, also long-chain. A medium chain base such as coconut or MCT oil would be absorbed more directly into portal blood and is markedly less lymphotropic, so the cocoa butter and apricot combination is better matched to this mechanism.
The lymphatic system is the immune compartment, holding the majority of the body's lymphocytes. The same research that demonstrated lipid-driven lymphatic uptake of cannabinoids also reported prominent immunomodulatory activity, assessed on lymphocytes drawn from multiple sclerosis patients and from cancer patients undergoing chemotherapy.10 A lipid-borne cannabinoid therefore does not merely reach the bloodstream, it concentrates in the tissue where immune regulation occurs, which aligns the delivery mechanism with the immunological intent of the line.
Cocoa butter is the structural matrix as well as the lymphotropic carrier. It requires approximately 80 per cent of total mass to hold its stable Form V crystal structure, which gives a firm suppository, clean demoulding and a predictable melt at body temperature. Liquid oil load above roughly 20 per cent of unit mass risks soft units, premature melting and phase separation. Apricot kernel oil provides the liquid long-chain lipid phase in which the cannabinoids are carried, ensuring uniform distribution through the unit and consistent release on melt. Both formulations sit inside that structural ceiling. The formulation carries no synthetic surfactant, since an additive intended to drive cannabinoids into the fast aqueous route would work against the lymphatic pathway rather than for it.
Foundation is the entry formulation and the default selection for patients without active autoimmune disease, active oncology or refractory chronic disease. It supports general endocannabinoid system regulation and is appropriate across the lifespan, including cannabinoid-naive patients, older adults, athletes, sensitive populations and men's and women's health applications.
A wellness and titration formulation. Foundation is the standard gateway for any patient intended for escalation to Advanced Care. It is used for initial assessment, for a defined reset course, and as long term maintenance following a course of Advanced Care.
Foundation is also dispensed as a defined reset for patients with no specific diagnosis who want to support endocannabinoid tone directly. The standard course is three months. A one month course is available for patients who want to assess response before committing, presented as a trial rather than a course. Patients who wish to continue may remain on Foundation indefinitely as maintenance.
| Patient profile | Detail |
|---|---|
| Hypersensitive patients | Patients who experience adverse reactions to standard cannabinoid doses including dizziness, fatigue, gastrointestinal discomfort or heightened sensitivity. Applies whether or not active disease is present, see the acclimatisation note below. |
| Older adults | Altered pharmacokinetics, polypharmacy considerations, frailty, or general age related sensitivity to therapeutic agents |
| Cannabinoid-naive patients | Any patient new to phytocannabinoid therapy requiring an introductory load before potential escalation to Advanced Care |
| Athletic recovery and performance | Athletes seeking inflammation control, recovery support, sleep quality and neuroprotection. Also lower body weight patients under 60 kg where proportional dosing is appropriate. |
| Mild chronic conditions | Mild inflammatory conditions, low grade chronic pain, mild anxiety, mild sleep disruption, early stage chronic disease, general immune support |
| Wellness and prevention | Patients without a specific diagnosis seeking endocannabinoid system support or general anti-inflammatory maintenance |
| ECS reset course | Healthy patients undertaking a defined one month or three month course to support endocannabinoid tone, with no active disease present |
| Post-treatment maintenance | Patients who have completed a course of Advanced Care and require ongoing endocannabinoid support and inflammation management |
| Titration gateway | Patients intended for Advanced Care who require a step-on entry point prior to escalation |
| Indication category | Specific presentations |
|---|---|
| Perimenopause | Brain fog, anxiety, mood instability, sleep disruption, cognitive symptoms, hormonal fluctuation |
| Menopause | Established menopause with night sweats, insomnia, anxiety, mood disorders, vaginal atrophy |
| Endometriosis | Confirmed or suspected endometriosis, endometrioma, adenomyosis, endometriosis related pelvic pain |
| Pelvic pain | Chronic pelvic pain, dysmenorrhoea, dyspareunia, pelvic inflammatory disease sequelae, interstitial cystitis, pelvic floor dysfunction |
| Hormonal mood disorders | PMS, PMDD, perimenopausal depression, hormonal anxiety, menstrual cycle related mood disorders |
| Gynaecological inflammation | Vulvodynia, vestibulodynia, vaginismus, chronic cervicitis, pelvic inflammatory disease |
Standard escalation protocol. Four weeks on Foundation with good tolerance, then progress to Advanced Care where active autoimmune, oncological, inflammatory or neurodegenerative disease is present. If symptoms are mild and the patient is satisfied on Foundation, continuation without escalation is appropriate. Because both formulations share the same cannabinoid profile, tolerance established on Foundation carries forward and escalation is a change of load rather than a change of preparation.
Disease burden is not the only thing that determines starting load. A patient may present with an indication that clearly sits in Advanced Care and still be a poor candidate to start there, because they are hypersensitive to cannabinoids generally or have reacted adversely to them before.
For those patients, begin on Foundation for the first four weeks regardless of diagnosis, then escalate to Advanced Care if tolerance is good. The four weeks serve as an acclimatisation period, allowing the endocannabinoid system time to adjust to a sustained phytocannabinoid load before the higher strength is introduced. Starting a hypersensitive patient directly on 400 mg risks an adverse response that ends the course altogether, and a patient who abandons therapy in week one gains nothing from a formulation matched perfectly to their diagnosis.
Treat this as the default where any of the following apply: a documented adverse reaction to cannabinoids at any dose, marked sensitivity to therapeutic agents in general, mast cell activation syndrome, significant polypharmacy, frailty, low body weight, or a patient who reports themselves as reacting strongly to medication. Where the patient is uncertain, the cautious route costs four weeks and nothing else.
Advanced Care is the therapeutic formulation of the line, carrying roughly three times the cannabinoid load of Foundation. It covers the full range of active disease from established autoimmune conditions through to palliative care.
It is intended for patients with a diagnosis requiring sustained intervention. Patients may step up from Foundation after four weeks, or enter directly where established active disease is present and the patient has prior cannabinoid experience. The formulation contains no Delta-8-THC, so it is suitable for patients in employment subject to drug screening and for paediatric oncology contexts under specialist supervision.
Hypersensitive patients begin on Foundation. Four weeks on the lower strength first, even where the diagnosis clearly indicates Advanced Care, as set out in the acclimatisation guidance in the previous section.
| Category | Specific indications |
|---|---|
| Solid tumours | Breast, colorectal, prostate, lung, head and neck, cervical, ovarian, bladder, kidney, liver, pancreatic, stomach, oesophageal, thyroid, skin including melanoma |
| Haematological cancers | Leukaemia including AML, CLL and ALL, lymphoma including Hodgkin's and non-Hodgkin's, multiple myeloma, myelodysplastic syndrome |
| Metastatic and stage 4 disease | Metastatic disease across all solid tumour types where maximum phytocannabinoid load is clinically warranted. Two suppositories daily is the usual protocol. |
| Refractory haematological disease | Refractory or relapsed leukaemia, lymphoma or multiple myeloma where conventional therapy has failed or is no longer tolerated |
| Adjunctive oncology support | Patients receiving chemotherapy, radiotherapy or immunotherapy seeking phytocannabinoid adjunctive support for inflammation, pain, nausea and immune modulation |
| Chemotherapy induced peripheral neuropathy | Severe CIPN requiring high load phytocannabinoid intervention |
| Paediatric oncology | Paediatric oncology contexts under specialist supervision. Dose proportional to body weight at practitioner discretion. |
The oncology positioning of this line rests on preclinical and mechanistic work rather than on clinical trial evidence. Antineoplastic activity of cannabinoids was first reported in NIH-funded work in 1975,31 and cell culture studies continue to report cytotoxic and antiproliferative signals for individual cannabinoids in the blend.30,32 None of that constitutes evidence that these suppositories treat cancer, and the formulation is offered only as an adjunct alongside conventional oncology care under practitioner supervision.
| Category | Specific indications |
|---|---|
| Rheumatological | Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, SLE, Sjogren's syndrome, systemic sclerosis, mixed connective tissue disease, polymyalgia rheumatica, giant cell arteritis, dermatomyositis, polymyositis |
| Neurological autoimmune | Multiple sclerosis, neuromyelitis optica, myasthenia gravis, Guillain-Barre syndrome, CIDP, autoimmune encephalitis |
| Gastrointestinal autoimmune | Crohn's disease, ulcerative colitis, coeliac disease, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, microscopic colitis |
| Endocrine autoimmune | Hashimoto's thyroiditis, Graves' disease, type 1 diabetes, Addison's disease, autoimmune polyglandular syndrome |
| Skin autoimmune | Psoriasis, lichen planus, vitiligo, pemphigus vulgaris, bullous pemphigoid, alopecia areata |
| Vascular autoimmune | Vasculitis including ANCA associated, Behcet's disease and Takayasu arteritis, antiphospholipid syndrome |
| Renal autoimmune | IgA nephropathy, lupus nephritis, membranous nephropathy, Goodpasture syndrome |
| Tick-borne and Lyme | Lyme disease acute and chronic, post-treatment Lyme disease syndrome, Lyme associated autoimmune arthritis, neurological Lyme, co-infections with Bartonella and Babesia where immune dysregulation is present |
| Other autoimmune | Sarcoidosis, relapsing polychondritis, Still's disease, undifferentiated connective tissue disease, reactive arthritis, SAPHO syndrome, chronic fatigue syndrome with autoimmune component, mast cell activation syndrome |
| End-stage and treatment resistant | Advanced MS, refractory SLE with significant organ involvement, severe Crohn's disease, treatment resistant rheumatoid arthritis, end-stage autoimmune hepatitis. Two suppositories daily is the usual protocol. |
The autoimmune rationale rests on TNF-alpha and CB2 engagement, on reported regulation of gene networks in autoimmune T cells,33 and on the immunomodulatory activity observed in the lymphatic transport work described in section eight.10
| Category | Specific indications |
|---|---|
| Post-infectious inflammation | Post-acute COVID inflammatory sequelae, post-viral inflammatory syndromes, post-infectious fatigue with inflammatory burden |
| Chronic pain syndromes | Fibromyalgia, complex regional pain syndrome, neuropathic pain with inflammatory component, post-surgical chronic pain, inflammatory chronic low back pain, failed back surgery syndrome |
| Systemic inflammatory conditions | Chronic systemic inflammation, metabolic inflammatory syndrome, cardiovascular disease with inflammatory burden, oxidative stress conditions |
| Inflammatory bowel disease | Active ulcerative colitis, Crohn's disease including colonic, ileocolonic and perianal, microscopic colitis, indeterminate colitis |
| Functional GI with inflammation | IBS with inflammatory component, post-infectious IBS, bowel dysmotility with inflammatory burden |
| Immune compromise | HIV and AIDS, post-transplant immune suppression, immunodeficiency disorders requiring immune modulation support |
| Treatment-resistant pain | Patients who have plateaued on Foundation or other cannabinoid therapies and require escalation. Suitable for opioid reduction candidates under practitioner guidance. |
Advanced Care is the formulation for neurodegenerative and neurological presentations. The dedicated Neuro Complex adjunct has been discontinued and its indications are covered here.
Neuro Complex was differentiated by its Delta-8-THC content, included for NMDA receptor modulation via GRIN2B. With Delta-8 withdrawn, that distinction no longer exists and the GRIN2B target is not engaged by any cannabinoid in the current line. The remaining pharmacology of the blend is delivered more completely by Advanced Care at a higher cannabinoid load. Practitioners who were combining Neuro Complex with a tier suppository should move those patients to Advanced Care alone.
| Condition | Clinical and mechanistic notes |
|---|---|
| Alzheimer's disease | All stages. The formulation engages cannabinoid receptor targets CNR1 and CNR2 alongside signalling targets AKT1, CASP9, PRKCA, PRKCB and CREB1. The DAZACANN trial, NCT07091747, using CBD with THC over 24 months is ongoing. Peer-reviewed studies report tau pathology attenuation in 5xFAD mice and reduction in dementia related agitation with cannabinoid extracts. |
| Parkinson's disease | All stages. The Chagas 2014 exploratory double blind trial showed quality of life improvement with CBD. A 2025 randomised controlled trial at Buriram Hospital used CBD with THC. The CBG quinone derivative VCE-003.2 showed PPAR mediated neuroprotection in the 6-OHDA model, which is of direct relevance given the CBG content of this formulation. |
| Lewy body dementia | Lewy body dementia, Parkinson's disease dementia and related alpha-synuclein pathologies |
| Frontotemporal dementia | Frontotemporal dementia, primary progressive aphasia, behavioural variant FTD |
| Vascular dementia | Post-stroke vascular dementia, small vessel disease dementia, mixed dementia |
| ALS and motor neurone disease | Published molecular docking research reports CNR1 binding at minus 9.4 kcal per mol for CBN, which is present in both formulations. Preclinical studies suggest neuroprotective activity relevant to ALS models. |
| Huntington's disease | A Sativex-like CBD with THC combination showed neuroprotective effects in the R6/2 transgenic mouse model. Two clinical trials, CBD in 1991 and Sativex in 2016, showed safety and tolerability without demonstrating efficacy. |
| Multiple system atrophy | Multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration |
The neurodegenerative literature for cannabinoids is largely preclinical, and the human trials that exist are small, mostly open label, and report safety and tolerability more consistently than efficacy.34,35 The DAZACANN study referenced in the table is the open label extension arm of a Brazilian trial, uncontrolled and unblinded, and should not be presented to patients as controlled evidence.
| Condition | Clinical notes |
|---|---|
| Stroke recovery | Post-stroke rehabilitation and cerebral ischaemia recovery. Peer-reviewed research suggests cannabinoid support of memory and neuroprotective pathways in cerebral ischaemia models. |
| Traumatic brain injury | TBI recovery at all stages, post-concussion syndrome, chronic traumatic encephalopathy |
| Spinal cord injury | Spinal cord injury with neurological sequelae, central sensitisation, spasticity |
| Post-viral neurological | Long COVID neurological symptoms, post-viral encephalitis, post-viral cognitive impairment, POTS with neurological involvement |
| Condition | Clinical notes |
|---|---|
| Multiple sclerosis | Relapsing remitting, secondary progressive and primary progressive MS. Sativex is approved for MS spasticity in a number of countries. Two suppositories daily where both neurological symptoms and systemic inflammatory burden are significant. |
| Neuroinflammation | Chronic neuroinflammation of any origin, autoimmune encephalitis, neuromyelitis optica, CNS vasculitis |
| Peripheral neuropathy | Diabetic neuropathy, chemotherapy induced peripheral neuropathy, idiopathic peripheral neuropathy, small fibre neuropathy |
| Epilepsy | Drug resistant epilepsy, Dravet syndrome, Lennox-Gastaut syndrome, focal onset seizures. Adjunctive to conventional anti-epileptic therapy only. |
| Neuropathic pain | Central and peripheral neuropathic pain, trigeminal neuralgia, post-herpetic neuralgia, phantom limb pain, complex regional pain syndrome |
| Memory and cognition | Age related cognitive decline, mild cognitive impairment, subjective cognitive decline, chemotherapy related cognitive impairment |
| Psychiatric with neurological basis | Treatment resistant depression with neuroinflammatory component, PTSD with neurological involvement, OCD, Tourette syndrome |
The epilepsy entry is the best evidenced indication in this section, though the human evidence is for oral CBD preparations rather than for this formulation or this route. Anticonvulsant activity has also been reported for cannabichromene in a Dravet model.36
Palliative and terminal care. Advanced Care at two suppositories daily is the standard protocol for any terminal diagnosis where maximum symptom support is the priority. Pain, inflammation, nausea, appetite and anxiety are addressed within a formulation containing no Delta-8-THC, so there is no drug screening consideration and no written advisory requirement.
| Formulation | Per unit | Frequency | Route | Drug screen |
|---|---|---|---|---|
| Foundation | 130 mg | 1 per day | Rectal only | Not expected to affect |
| Advanced Care | 400 mg | 1 to 2 per day | Rectal only | Not expected to affect |
| Presentation | Formulation | Protocol |
|---|---|---|
| No active disease, wellness or reset | Foundation | 1 daily, one or three months |
| Cannabinoid-naive, any destination | Foundation first | 1 daily for four weeks, then review |
| Sensitive, elderly or low body weight | Foundation | 1 daily, maintain |
| Women's health presentations | Foundation | 1 daily, six to twelve months |
| Hypersensitive, any diagnosis | Foundation first | 1 daily for four weeks, then escalate |
| Active autoimmune or inflammatory disease | Advanced Care | 1 daily |
| Oncology adjunct, stage 1 to 3 | Advanced Care | 1 daily |
| Stage 4, refractory or palliative | Advanced Care | 2 daily, morning and evening |
| Neurodegenerative disease | Advanced Care | 1 to 2 daily by disease burden |
| Completed a course of Advanced Care | Foundation | 1 daily as maintenance |
Standard administration is one suppository rectally each evening. Two suppository daily dosing, morning and evening, may be appropriate in advanced and refractory presentations. Suppositories are for rectal use only and must not be taken orally. Store below 25 degrees Celsius, since CBDa and CBGa decarboxylate on warming and the acidic fraction is where much of the anti-inflammatory profile sits.
Cannabinoids in these formulations inhibit CYP2C9 and CYP3A4. Review the patient's medication list for substrates of these enzymes, including warfarin, certain statins, calcium channel blockers, immunosuppressants and chemotherapeutic agents, and monitor accordingly. This is the most clinically consequential caution in the document and applies at both strengths, more so at Advanced Care.
CBN may potentiate the sedative effect of opioids and benzodiazepines. Because Advanced Care carries approximately 57 mg of CBN per suppository, evening administration is preferred and patients on sedating medication should be counselled accordingly.
Total THC in both formulations is below the federal limit of 0.4 mg per container that takes effect on 12 November 2026, on worst case arithmetic charging the base material at its laboratory limit of detection. Each production batch is verified by certificate of analysis. Practitioners should request the batch certificate for any lot dispensed.
Every link below was opened and confirmed to resolve. 28 of the 34 sources are open access, meaning the full text is readable by anyone with no login, payment or institutional subscription. The remaining 6 are marked abstract only, where the publisher holds the full text behind a paywall and no legitimate free version exists. Where the strongest source was paywalled, a freely readable paper covering the same compound and mechanism has been given instead and identified as such.
| CBD, cannabidiol | The principal non-psychoactive cannabinoid. Acts indirectly on the endocannabinoid system and on several other receptors. |
| CBG, cannabigerol | A minor cannabinoid that partially activates the cannabinoid receptors. Studied for neuroprotection and inflammation. |
| CBN, cannabinol | A cannabinoid formed as THC ages. The strongest binder of the CB1 receptor in this set, sedative and immune active. |
| CBC, cannabichromene | A cannabinoid acting at the CB2 receptor and at sensory ion channels. One of the few with nerve cell growth activity. |
| CBDa, cannabidiolic acid | The raw, acidic form of CBD found in the unheated plant. A strong anti-inflammatory binder. |
| CBGa, cannabigerolic acid | The acidic form of CBG. Anti-inflammatory and metabolic targets. |
| CBDV, cannabidivarin | A close chemical relative of CBD. Non-psychoactive, studied for seizures. |
| CBE, cannabielsoin | A natural breakdown product of CBD with little defined pharmacological activity. |
| CBTC, cannabicitran | A minor cyclised cannabinoid with little defined pharmacological activity. |
| CBL, cannabicyclol | A natural conversion product of CBC with no significant defined activity. |
| THC | The main psychoactive cannabinoid. Not detected in the base material used in this line. |
| CRD, crystal resistant distillate | A hemp extract processed to stay liquid rather than crystallise, which necessarily means it has retained a high proportion of minor cannabinoids. |
| Isolate | A single cannabinoid purified to near 100 per cent, with everything else removed. |
| Broad spectrum | An extract containing many cannabinoids but with THC reduced to undetectable levels. |
| Entourage effect | The principle that cannabinoids and related plant compounds act more effectively together than any one does alone. |
| Decarboxylation | The heat-driven loss of an acidic cannabinoid's acid group, converting CBDa to CBD. The reason acidic cannabinoids need cool storage. |
| ECS | The body's balancing signalling network spanning the nervous, immune and other systems. |
| CB1 (CNR1) | The cannabinoid receptor concentrated in the brain and nerves. |
| CB2 (CNR2) | The cannabinoid receptor concentrated in immune and peripheral tissue. |
| Endocannabinoids | The body's own cannabinoid-like signalling molecules, chiefly anandamide and 2-AG. |
| FAAH, MAGL | The enzymes that break down anandamide and 2-AG respectively. |
| Endocannabinoid tone | The resting level of activity in the endocannabinoid system. |
| Agonist, partial agonist | A molecule that activates a receptor. A partial agonist activates it only partway. |
| Allosteric modulator | A molecule that changes how a receptor responds without binding its main site. |
| TRPV1, TRPA1, TRPM8 | Temperature and irritant sensing ion channels involved in pain and inflammation. |
| GPR55 | A receptor sometimes described as a third cannabinoid receptor. |
| PPAR, PPAR-gamma | A nuclear receptor regulating metabolism and inflammation. |
| 5-HT1A | A serotonin receptor involved in mood and anti-anxiety effects. |
| Network pharmacology | Mapping how a compound acts across many protein targets at once, rather than at a single target. |
| Molecular docking | A computer simulation that estimates how tightly a molecule binds a protein. A prediction, not a measurement. |
| Binding affinity (kcal/mol) | The strength of that predicted binding. A more negative number means stronger binding. |
| Degree centrality | How many targets a molecule connects to in the network. High centrality means broad action. |
| TNF-alpha | A central inflammatory signalling protein and a major target in autoimmune disease. |
| AKT1, CASP9, PRKCA, PRKCB, PLCG1 | Cell survival, cell death and cell cycle proteins relevant to cancer signalling. |
| CYCS, cytochrome c | A protein central to the programmed cell death pathway. |
| COMT | An enzyme in dopamine metabolism, relevant to Parkinson's disease. |
| CAT, GSTA2, GSTM3, GSTP1, HMOX1 | Antioxidant and detoxification proteins that handle oxidative stress. |
| CREB1 | A gene regulation protein involved in memory and neuron survival. |
| GRIN2B, NMDA receptor | A glutamate receptor subunit involved in nerve over-stimulation in neurodegenerative disease. Not engaged by any cannabinoid in the current line. |
| COX-2 | The inflammation enzyme targeted by common anti-inflammatory drugs. |
| CYP2C9, CYP3A4 | Liver enzymes that process many medicines. Cannabinoids inhibit them, which is the basis for the drug interaction caution. |
| Bioavailability | The fraction of a dose that actually reaches the bloodstream. |
| First-pass metabolism | The loss of an orally absorbed drug to the liver before it reaches the rest of the body. |
| Lipophilic | Fat-loving. Dissolves in oil rather than water. Cannabinoids are strongly lipophilic. |
| log P | A number describing lipophilicity. Above 5 indicates strong fat solubility and the potential for lymphatic transport. |
| Lymphatic transport | Absorption of fat-soluble molecules through the lymphatic system, which bypasses the liver. |
| Chylomicrons | The fat-carrying particles that ferry lipophilic molecules into the lymph. |
| Long-chain triglyceride | A long fatty acid type that drives lymphatic absorption. Cocoa butter and apricot kernel oil are long-chain. |
| Medium-chain triglyceride | A shorter fatty acid type such as coconut oil, absorbed mainly into the blood and far less lymphotropic. |
| Portal vein | The vein carrying gut-absorbed substances to the liver. |
| Form V | The stable crystal form of cocoa butter that gives a firm suppository and clean release. |
| COA, certificate of analysis | The laboratory report verifying a material's contents and purity. |
| ISO/IEC 17025 | The international standard for the competence of testing laboratories. |