Throughout history, the cannabis plant has been used for a wide range of therapeutic purposes, including for pain relief. While much of the public discussion around cannabis focuses on cannabidiol (CBD) and tetrahydrocannabinol (THC), the plant contains hundreds of other compounds known as “minor” cannabinoids.
Understanding Neuropathic Pain
Neuropathic pain (pain caused by nerve damage or disease) involves enhanced sensitivity as a result of changes in nociceptive ion channel and receptor expression. It may occur as a result of conditions such as diabetes or multiple sclerosis (MS), or due to injury or surgery.
Neuropathic pain is often characterised by symptoms such as burning, shooting, or tingling sensations, as well as muscle weakness and extreme sensitivity to touch.
Treatment of neuropathic pain usually requires a multifaceted approach, which may involve a combination of medications, including addressing the underlying cause if possible, talking therapies, physiotherapy and if necessary medications. In neuropathic pain, whilst many people may be prescribed conventional pain medications such as paracetamol, non-steroidal anti-inflammatories and opioids, people are most commonly prescribed neuropathic pain agents.
These medications include gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, and anti-epileptic drugs.
Cannabinoids and Neuropathic Pain
Cannabis and its derivatives have been implicated as a potential therapeutic option for pain management; however, evidence of their benefit for neuropathic pain relief is variable, warranting further investigation to determine their long-term effects.
Preclinical studies have yielded promising results and there is increasing clinical data on the effects of the major cannabinoids. However, there is little information available regarding the potential of lesser-known or “minor” cannabinoids in relation to pain signalling. A recent study led in part by Curaleaf International, looked into how ten of these lesser-known cannabinoids might affect nerve cells that have become overly sensitive (neuronal hypersensitivity). This hypersensitivity is a key mechanism that underlies neuropathic pain.
How the Study Explored Pain Signalling
The researchers used an in vitro (a petri dish) model, which is a common way to study cell behaviour in a controlled environment.
- Sensitising Nerve Cells: Sensory nerve cells, called dorsal root ganglion (DRG) neurons, were taken from adult rats and grown in a dish. These cells sense pain in the body. They were treated with nerve growth factor and glial cell-line-derived neurotrophic factor for 48 hours, to make them extra sensitive, simulating the enhanced signalling seen in neuropathic pain.
- Stimulating Pain Signals: Capsaicin, the compound that makes chilli peppers hot, was used to intentionally stimulate a key pain receptor on the nerve cells, called transient receptor potential cation channel subfamily V member 1 (TRPV1). This stimulation triggers a rush of calcium ions into the cell causing a signal
- Testing Minor Cannabinoids: Ten minor cannabinoids were applied to the nerve cells before the capsaicin was added. This included tetrahydrocannabiorcol (THCC), cannabinol (CBN), cannabitriol (CBT), cannabichromene (CBC), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabicitran (CBTC), cannabigerol monomethyl ether (CBGM), tetrahydrocannabutol (THCB), and tetrahydrocannabiphorol (THCP).
Key Findings
The results showed that, in this laboratory model, all ten of the minor cannabinoids tested were able to block the capsaicin-triggered calcium influx.
- Blocking the Signal: In a significant percentage of the capsaicin-sensitive nerve cells (ranging from 35% to 78%), the cannabinoids completely inhibited the immediate calcium ion influx
- Comparison to Standard Medicines: The effects were compared to the established neuropathic pain medicines, which showed similar inhibitory effects. Some of the cannabinoids even appeared to inhibit the pain signal in a greater number of nerve cells than gabapentin or morphine in this in vitro assay.
- Cannabichromene (CBC) Mechanism: The research found that CBC appeared to block the pain signal by working through the cell’s potassium ion channels. When researchers applied a potassium channel blocker, CBC’s inhibitory effect was reversed, allowing the capsaicin-induced calcium influx to return. This suggests that CBC’s action may involve activating these potassium ion channels, which can quieten the over-excitable nerve cells.
- Biphasic Effects: Two of the cannabinoids, THCC and CBN, also showed a dual effect. While they mostly inhibited the pain signal at lower doses, they also caused a calcium io influx at higher concentrations.
What Does This Tell Us?
This study is a crucial step in understanding how minor cannabinoids might interact with the pain signalling pathways in nerve cells. The researchers concluded that all the cannabinoids tested inhibited the TRPV1 signalling in the sensitised neurons. The distinct mechanism identified for CBC, involving potassium ion channel activation, highlights a potential target for investigation.
This research was conducted in a laboratory dish using rat nerve cells, not in human patients. While these preclinical results are encouraging and suggest areas for further exploration, they do not prove that these compounds are effective or safe for treating pain in humans. Further studies are necessary to confirm these mechanisms and to determine if these compounds or their combinations can be helpful for chronic pain relief in a clinical setting.
If you are interested in learning more about the medicinal use of cannabis-based products, including their potential in conditions like neuropathic pain, the first step is to speak with a specialist clinician.
