The Therapeutic Effectiveness of Full Spectrum Hemp Oil Using a Chronic Neuropathic Pain Model
Background: Few models exist that can control for placebo and expectancy effects commonly observed in clinical trials measuring ‘Cannabis’ pharmacodynamics. We used the Foramen Rotundum Inflammatory Constriction Trigeminal Infraorbital Nerve injury (FRICT-ION) model to measure the effect of “full-spectrum” whole plant extracted hemp oil on chronic neuropathic pain sensitivity in mice. Methods: Male BALBc mice were submitted to the FRICT-ION chronic neuropathic pain model with oral insertion through an incision in the buccal/cheek crease of 3 mm of chromic gut suture (4-0). The suture, wedged along the V2 trigeminal nerve branch, creates a continuous irritation that develops into secondary mechanical hypersensitivity on the snout. Von Frey filament stimuli on the mouse whisker pad was used to assess the mechanical pain threshold from 0–6 h following dosing among animals (n = 6) exposed to 5 μL of whole plant extracted hemp oil combined with a peanut butter vehicle (0.138 mg/kg), the vehicle alone (n = 3) 7 weeks post-surgery, or a naïve control condition (n = 3). Results: Mechanical allodynia was alleviated within 1 h (d = 2.50, p < 0.001) with a peak reversal effect at 4 h (d = 7.21, p < 0.001) and remained significant throughout the 6 h observation window. There was no threshold change on contralateral whisker pad after hemp oil administration, demonstrating the localization of anesthetic response to affected areas. Conclusion: Future research should focus on how whole plant extracted hemp oil affects multi-sensory and cognitive-attentional systems that process pain.
The enactment of the Hemp Farming Act, effectively beginning in 2019, was a monumental milestone in the history of Cannabis prohibition in the United States (U.S.), because it enabled the legal consumption, commercial production, and market trade of any type of product made from certain variants of the Cannabis plant. Only differing from their federally illegal counterparts, arbitrarily defined as Cannabis plants containing over 0.3% tetrahydrocannabinol (THC) potency levels, the legal variety of the Cannabis plant—conventionally referred to as ‘hemp’—still contains hundreds of additional phytochemicals, including cannabinoids (e.g., cannabidiols, CBDs), terpenes, terpenoids, and flavonoids that may offer potent therapeutics, both individually and synergistically [1,2,3,4]. Despite widespread Cannabis usage in the U.S., with estimated annual revenues now in the tens of billions of dollars, current patients and providers still have little scientific evidence on the likely effectiveness of common and commercially available cannabis-based products for pharmaceutical application. This is because the federal government has largely limited clinical investigations to plant-inspired isolates, concocted formulants, or synthetic analogues not representative of the whole, natural Cannabis plant-based products most widely used by millions of people in the U.S. [5,6]. Another frequent and unavoidable limitation of extant human trials measuring Cannabis’ pharmacodynamics is that they cannot control for placebo and expectancy effects, or visceral, perceptual, and/or cognitive reactions to enrollment in a cannabis-themed experiment, with several studies observing Cannabis-related experiences reported by both active agent and placebo group participants [7,8].
While animal models can control for expectancy effects, few paradigms have created a persistent state of chronic pain, with the majority of conventional pain models resulting in a recoverable, and hence qualitatively different forms of pain than one that is ‘chronic’ in nature, and hence often and uniquely tethered with comorbid affective disturbances (e.g., depression) [9,10]. One well-established and reliable chronic pain model, the Foramen Rotundum Inflammatory Constriction Trigeminal Infraorbital Nerve injury (FRICT-ION) model involves an insertion of 3 mm of chromic gut suture (4-0) along the maxillary branch as it passes into the foramen rotundum through a tiny scalpel incision in the buccal/cheek crease . Mechanical hypersensitivity reliably develops on the snout persisting through >100 days, likely due to consistent inflammatory response caused in part by movement of the nerve during chewing. The extended 3–10 week timeframe for study allowed by the FRICT-ION model is reportedly equivalent to 5–8 years of chronic pain in clinical patients [12,13].
Studies examining the neuropharmacology of neuropathic pain have implicated opioid (e.g., MOP/DOP) [14,15,16], serotonin (e.g., 5-HT7) [17,18], dopamine (e.g., D2) [19,20] and glutamate (e.g., GluN2B) [21,22,23] receptor systems as potential therapeutic targets; however, no studies to date have examined the effects of whole plant-extracted hemp oil on chronic pain. Therefore, in the present study, we investigated the analgesic effects of “full-spectrum” whole plant oil extracted from the hemp plant, using ethanol and evaporation-based procedures commonly used in the Cannabis industry, on mechanical neuropathic chronic pain sensitivity in mice. By creating a continuous state of irritation in the infraorbital nerve, the FRICT-ION mouse model of chronic orofacial neuropathic pain can initiate mechanical allodynia in the mouse whisker pad for pharmaceutical investigation. We use a standard von Frey test for mechanical hypersensitivity at 7 weeks post-surgery to measure the effects of orally administered hemp oil over a 6 h observation window, in comparison to vehicle only and naïve control mice, to estimate the general efficacy of commonly used hemp-based products for therapeutic application.
2. Materials and Methods
2.1. Experimental Plan
The general experimental plan is shown in Figure 1 .
Model induction began 1 week after acclimatization of the male mice. The animals were tested weekly for mechanical sensitivity with von Frey fibers applied to the whisker pad. Hypersensitivity was induced within the first week and continued indefinitely. After the week 7 testing, mice with FRICT-ION nerve compression neuropathic pain were given either hemp oil mixed in peanut butter (0.138 mg/kg) or peanut butter alone. Naïve control mice received weekly behavioral testing.
Subjects were 12 male BALBc mice (20–30 g, Envigo) housed in the animal housing facility of the University of New Mexico Health Science Campus. Mice were housed in groups of 3 per cage, with food and water available ad libitum, in a temperature-controlled room (23 °C) under a reversed 12 h/12 h light/dark cycle (lights on at 7:00 PM). The mice were transported to the experimental room in their home cages and left undisturbed for 1 h prior to testing. All efforts were made to minimize animal stress and suffering, and to reduce the number of mice used. The experiment received formal approval from the Committee on Animal Research and Ethics, Health Sciences Center, University of New Mexico (IACUC #17-200613). The experiment reported in this article was performed in accordance with the recommendations of the United States National Institutes of Health Guide for the Care and Use of Laboratory Animals and the guidelines of the Committee for Research and Ethical Issues of the International Association for the Study of Pain .
2.3. Surgical Procedures for Induction of the Model
The surgical model induction has been described in detail previously . Briefly, mice were anesthetized with isoflurane (2%) and then a small surgical incision was made orally between the cheek and maxillary bone. A chromic gut suture (4.0, 3 mm) was inserted into the tight space between the infraorbital (ION) trigeminal nerve branch and the bony foramen rotundum as the nerve enters the skull. The anesthesia and surgery took less than 5 min. All surgeries were performed in sterile conditions under a surgical microscope.
Whisker pad hypersensitivity developed reliably and persisted for at least 3 months [11,25]. In sham operations reported in a previous full description of the procedure, the ION was exposed but not compressed . All animals underwent weekly behavioral testing to confirm mechanical threshold level and sham animals responded like naïve animals after recovery from the sham surgery ( Figure 1 and Figure 2 A). Estimates are that in week 8, mice had experienced pain equivalent to several human years and can be considered chronic [12,13]. Group comparisons included naïve and neuropathic pain groups, with and without hemp oil. All studies were blinded.
Mechanical hypersensitivity in a chronic trigeminal neuropathic pain model and effects of hemp oil. (A) Effect of trigeminal nerve injury. The reduction in mechanical threshold latency response to von Frey fiber mechanical stimulation of the whisker pad is statistically significant for 12 weeks after FRICT-ION trigeminal nerve compression injury. (B) Effect of hemp oil ingestion. The efficacy of hemp oil administered in peanut butter was tested in week 7 post nerve injury in male mice. Mechanical threshold was tested hourly on the ipsilateral whisker pad. The data are presented as a mean ± SEM. Two-way ANOVA with Dunnett’s multiple comparisons test. For the graphs, asterisks (*) indicate p < 0.05 comparing the FRICT-ION + Hemp to naïve control and (***) p < 0.001 comparing the FRICT-ION to naïve control. Dagger (†) indicates p < 0.05 comparing the FRICT-ION + Hemp to FRICT-ION.
2.4. Assessment of Mechanical Allodynia
Post-surgery mechanical sensitivity of the whisker pad was determined in the infraorbital nerve receptive field with a series of 8 von Frey fiber filaments (0.008 g (1.65); 0.02 g (2.36); 0.07 g (2.83); 0.16 g (3.22); 0.4 g (3.61); 1.0 g (4.08); 2.0 g (4.31); 6.0 g (4.74); Stoelting, Wood Dale, IL, USA) by the modified up-down method . Mice were handled several times before experiments and were trained in the procedure for one week prior to the actual test. The experimenter held the mouse with a cupped hand until the animal was calm. Mice moved freely in the holder’s hands with its head exposed. During testing, the experimenter slightly restrained the mouse in their hand while accurately applying the von Frey filament onto the center of the mouse whisker pads, both ipsilateral and contralateral to the surgery site. For the consistency of results, each filament was applied five times at intervals of a few seconds. If head withdrawal was observed at least three times after probing with a filament, the mouse was considered responsive to that filament according to the up-down method . For this approach, whenever a positive response to the mechanical stimulus occurred, the next weaker von Frey filament was applied. If no positive response was evoked, the next stronger filament was applied. Testing proceeded in this manner until four fibers applied after the first one successfully caused positive responses. This allowed estimation of the 50% mechanical withdrawal threshold (in grams force) using a curve-fitting algorithm. Baseline assessment of nociception was done in week 2 after acclimatization. After surgical induction of the FRICT-ION model, testing for hypersensitivity was done once weekly through to week 12.
2.5. Hemp Oil Dosing
Prior to testing the effects of hemp oil on the behavioral changes, mechanical allodynia was confirmed in the mice in weeks 1–6 after induction of the nerve trauma and re-tested in week 7, prior to the experiment ( Figure 2 A). The mechanical pain threshold was measured hourly (0–6 h) following dosing among animals exposed to 5 μL of hemp oil dissolved in peanut butter as the vehicle (0.138 mg/kg; n = 6), the peanut butter vehicle alone (n = 3), or a naïve control condition (n = 3) ( Figure 2 B). The naïve mice underwent all procedures and tests except the surgery. The animals immediately ate the peanut butter with or without the hemp oil. The mechanical threshold on the whisker pad on the side of the inflamed nerve and on the contralateral side was assessed hourly after consumption for 6 h.
2.6. Hemp Cultivation and Oil Extraction
The hemp oil was cultivated by Organic-Energetic Solutions LLC (Albuquerque, NM, USA) and commercially available under the “LyFeBaak” label. The oil is derived from “Cherry Blossom” hemp plants that have been cultivated using proprietary methods that hypermineralize the plants throughout the vegetative and flowering phases of cultivation. The cannabinoid and terpene analytics of the Cherry Blossom plants used to produce the hemp oil are shown in Table 1 and Table 2 , respectively. Mature Cannabis hemp buds were used in an alcohol bath extraction procedure using ethanol as a solvent. The procedure stripped the cannabinoids, terpenes, chlorophyll, fats, lipids and wax compounds from plant material by suspending those compounds in an alcohol solution form. The solution was then separated from the plant material using a strainer and the alcohol solution was further filtered until it was free of particulates. The alcohol was evaporated out of the solution, leaving a highly concentrated form of the botanical components harvested from the Cannabis plants, which was then combined with medium-chain triglyceride (MCT) oil in its final (retail) form. In the current study, 5 μL of hemp oil were combined with peanut butter (0.138 mg/kg) for the active agent group.
Cherry Blossom cannabinoid analytics.
|Phytochemical||% Total Weight||mg/g|
|Cannabigerolic Acid (CBGA)||0.281||2.810|
|Cannabidiolic Acid (CBDA)||14.464||144.640|
|Tetrahydrocannabinolic acid (THCA)||0.661||6.610|
Cherry Blossom terpene analytics.
|Phytochemical||% Total Weight||mg/g|
Note. Only detectable terpenes at levels greater than 0.007% are shown above. Terpenes with non-detectable levels include: alpha-cedrene, alpha-terpinene, beta-pinene, borneol, camphene, camphor, caryophyllene oxide, cedrol, sabinene, sabinene hydrate, terpineol, terpinolene, trans-nerolidol, valencene, pulegone, alpha-phellandrene, ocimene, nerol, linalool, geranyl acetate, geraniol, gamma-terpinene, fenchone, eucalyptol, isoborneol, hexahydrothymol, fenchyl alcohol, 3-carene, cis-nerolidol, isopulegol.
2.7. Statistical Analysis
The Prism 4 statistical program was used for data analysis (Graph Pad Software, Inc., La Jolla, CA, USA). All data were expressed as mean ± SD. The hourly changes in pain threshold following drug consumption were analyzed by one-way ANOVA followed by Tukey’s multiple comparison post hoc tests. A p ≤ 0.05 was considered significant.
The naïve group of mice responded throughout the testing period only to von Frey fibers which apply 6.000 g force (blue line, Figure 2 ) (6.000 ± 0.000). This was considered the baseline response. The development and continuation of whisker pad hypersensitivity in the untreated group is shown in Figure 2 A,B as the red line, indicating a response threshold to a von Frey fiber with minimal grams force (0.008 g) (0.067 ± 0.029). A repeated measures ANOVA showed a significant group–time interaction, F (2,9) = 17.65, p < 0.001). The treated group had the same response as the untreated group initially prior to the administration of the hemp oil, but the response reversed toward baseline stably between 2–4 h ( Figure 2 B green line). The response thresholds showed a bell-shaped dose-response curve in the treated group, but did not change over the 6 h observation period for the naïve and untreated groups (p > 0.10 in each case).
The results indicate the efficacy of the drug treatment in the chronic trigeminal neuropathic pain model. As shown in Figure 2 B, mechanical withdrawal threshold assessment indicated relief from hypersensitivity following hemp oil treatment at 1 (d = 2.50, p < 0.001), 2 (d = 3.44, p < 0.001), and 6 h (d = 2.20, p < 0.001), with a peak reversal of allodynia at 4 h (d = 7.21, p < 0.001). No adverse events were observed.
There is an urgent need for novel, alternative, opioid-sparing pain medications . To date, a growing body of evidence supports the use of Cannabis-based medicines for modulating analgesic, anti-inflammatory and anxiolytic effects [28,29,30,31,32,33,34], with chronic pain being the most widely cited health condition for medical Cannabis usage [5,35,36,37]. The current findings are consistent with clinical research among chronic pain patients  and large population-based studies measuring the real-time effects of Cannabis consumption on momentary pain intensity [39,40], which show that Cannabis is an effective mid-level analgesic. However, the current study is unique in measuring the effect of full spectrum hemp-extracted oil with negligible THC levels. Using an established and reliable chronic pain mouse model, we circumvented the unavoidable confound of human reactivity present in all clinical trials, and showed that 5 μL of legal hemp oil is a potent analgesic, reducing mechanical pain sensitivity over tenfold. The FRICT-ION model is an improvement over other trigeminal nerve injury models [41,42]. The model is minimally invasive, is induced in 5–10 min, reducing anesthetic exposure, persists indefinitely, and can easily be blinded compared to other surgical models where the animals have external sutures and shaved fur [41,42]. The current study builds on studies measuring the therapeutics of isolated or formulated cannabinoids, and most popularly, CBD , by showing that common and commercially available full spectrum oil extracted from the hemp plant, using techniques that are generally replicable and accessible to the layperson, may be an effective treatment for chronic pain caused by mechanical pressure. The study addresses the therapeutic value of hemp using an in vivo pain model that mimics injury to the trigeminal nerve and causes pain behaviors analogous to human chronic neuropathic pain . Pain arising from insult to the maxillary division of the trigeminal nerve has been lauded as a good predictor of efficacy for pain therapeutics that are later guided through FDA approvals . However, given that chronic pain remains a significant clinical challenge with a conventional treatment response rate of only 11% [46,47], the current findings show promising support for the effectiveness of a recently legalized (in the U.S.) alternative ethnopharmaceutical option for the treatment of some forms of chronic pain.
One of the most widely studied constituents of the Cannabis plant, CBD, may attenuate pain through several mechanisms of action. Although not fully characterized, the pharmacodynamic profile of CBD is diverse, producing agonistic and antagonistic effects at multiple cannabinoid and non-cannabinoid receptor sites. For instance, despite somewhat low affinity for the orthosteric binding sites, at low nanomolar doses, CBD is a non-competitive negative allosteric modulator at CB1 receptors [48,49,50] and an inverse agonist at CB2 receptors [49,51,52]. Additional non-cannabinoid mechanisms of CBD action include: (1) agonism at serotonin-1A (5-HT1A) [53,54] and transient receptor potential cation (e.g., calcium) channels subfamily V member types 1 and 2 (TRPV1-2) receptors [55,56,57], (2) positive allosteric modulation at gamma amino butyric acid (GABAA)  and glycine receptors , (3) antagonism of voltage-gated Cav2.2 calcium channels  and sigma-1 receptors , and (4) indirect endocannabinoid agonism by increasing levels of N-arachidonoylethanolamine (AEA) via blocking reuptake and inhibiting breakdown by FAAH .
Based on previous reports, the analgesic effects of CBD detected in the present study likely involve mixed effects at various receptor types. For instance, CBD prevents paclitaxel-induced allodynia and carrageenan-induced thermal hyperalgesia, effects that are reversed by the 5-HT1A antagonist WAY 100635  and the TRPV1 antagonist capsazepine , respectively. Interestingly, the effects of CBD on thermal hyperalgesia do not involve activity at CB1 or CB2 receptors as selective CB antagonists do not prevent the antihyperalgesic effects of CBD. Similarly, repeated CBD administration for 7 days reduces spared nerve injury (SNI)-induced mechanical allodynia, which is prevented by capsazepine or WAY 100635 . CBD antagonism of presynaptic Cav2.2 calcium channels  could also partially explain the present results, as selective CaV2.2 antagonists inhibit nociceptive signaling and reduce allodynia . CBD also enhances morphine-evoked supraspinal antinociception in the tail-flick task, effects that depend on CBD antagonism of sigma-1 receptors . CBD also reduces both CFA-induced inflammatory pain, surgical injury induced pain, and SNI-induced neuropathic pain, analgesic effects that depend on activation of the glycine alpha3 receptor [43,65]. Cannabidiolic acid (CBDA) and tetrahydrocannabinolic acid (THCA), the first and second most abundant cannabinoids (relatively) in the hemp plants used to produce the oil, have not been extensively investigated for their therapeutic value, due in part to their molecular instability, but have both been shown to influence nociceptive and nonnociceptive mechanoreceptors [66,67]. Collectively, these preclinical data indicate that CBD produces analgesic effects by altering signaling at multiple receptor systems and highlight the potential clinical utility of CBD for treating chronic pain.
In addition, terpenes such as β-myrcene, α-Pinene, and β-caryophyllene have been shown to exert anti-inflammatory and antinociceptive activities . While CBD exerts prolonged immunosuppression and might be used in chronic inflammation, terpenes demonstrate a transient immunosuppression and relieve acute inflammation . In our study, out of a total of 38 terpenoids tested, accounting for 0.65% of the hemp’s molecular weight, the eight most prominent terpenoids were: β-myrcene 0.256%, β-caryophyllene 0.121%, farnesene 0.080%, α-pinene 0.48%, guaiol 0.043%, α-bisabolol 0.040%, α-humulene 0.036%, and D-limonene 0.022%. Of these eight terpenoids, three have been shown to have either anti-inflammatory or antinociceptive properties, or both, and to be at a concentration of approximately 0.05% or greater, which is considered to be of pharmacological interest .
The monoterpene β-myrcene is one of the most prominent terpenes found in Cannabis and the most prominent terpene in the plants used to extract the hemp oil. It is often associated with sedating chemovars of cannabis, commonly referred to as “indicas.” β-myrcene has been shown to have high antinociceptive properties , and can be found in relatively high concentrations in plants such as lemongrass (Cymbopogon citratus), making up roughly 15% of dried product mass . β-caryophyllene, in contrast, is one of the most common sesquiterpenoids found in Cannabis and the second most prominent terpenoid in the plants used to make the hemp oil. Various species from the genus Copaifera contain high concentrations of either β-caryophyllene or caryophyllene oxide (a metabolite of β-caryophyllene) , and have been shown to possess anti-inflammatory and analgesic properties . While the exact mechanisms in which β-caryophyllene exerts its anti-inflammatory and antinociceptive properties are not fully understood, at least part of its mechanism of action is related to selective CB2 receptor agonism with no significant affinity for the CB1 receptor .
Finally, α-pinene is the most widely distributed terpenoid in nature and the fourth most prominent terpene in the Cherry Blossom plants used to make the hemp oil. In one study, α-pinene has been shown to significantly decrease lipopolysaccharide (LPS) induced production of nitric oxide, as well as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), which are both pro-inflammatory cytokines. α-Pinene inhibited inducible nitric oxide synthase (iNOS) as well as cyclooxygenase-2 (COX-2) expression in LPS-stimulated macrophages . In another study, an essential oil derived from the leaves of the black Chilean guava (Ugni myricoides) was analyzed and found to contain 52.1% α-pinene. The other constituents were 1,8-cineole (11.9%), α-humulene (4.6%), caryophyllene oxide + globulol (4.5%), humulene epoxide II (4.2%) and β-caryophyllene (2.9%) . The essential oil was able to significantly prevent mechanical hypernociception induced by complete Freund’s adjuvant (CFA) in mice. Both the full spectrum essential oil and isolated α-pinene were able to abolish the mechanical sensitization induced by CFA or following the partial ligation of the sciatic nerve. The efficacy of the essential oil was described to be similar to that observed for indomethacin or gabapentin and thus of potential interest for the treatment of inflammatory and neuropathic pain .
The current study has several limitations, including the measurement of a single product derived by a single strain of hemp, rendering a comparison across different chemovars impossible. It is also not entirely clear if the results are consistent with combustion, intravenous and/or intramuscular dosing and future studies should examine the pharmacodynamics and pharmacokinetics of various types of consumption. Another general challenge for the health and scientific communities is the lack of standardization across natural Cannabis-based products due to the heterogeneous nature of ethnopharmaceuticals and individual differences in their pharmacodynamics, which can be affected by variability in metabolic, diurnal, and enzymatic functioning, as well as distinctions across individual’s microbiomes at the time of dosing. It is also unclear how the current results translate comparatively, given that human pain sensations can be affected by not only tissue damage (e.g., physical disease and injury) and nociception within the peripheral and central nervous systems (e.g., modulating afferent input), but also cognitive percepts and visceral sensations, moods, and situational and contextual factors such as social settings [77,78,79,80,81]. Finally, given the small sample and observational nature of the current research design, caution may be warranted when interpreting the generalizability of the findings and/or application to human conditions. Future research will benefit by comparing whole plant extracted hemp oil effects with dose-response curves of some of the main compounds present in the oil to verify the utility of full spectrum therapeutics.
The present study shows for the first time that common, commercially available, and easily reproducible full-spectrum hemp oil induces significant anti-allodynic effects with a bell-shaped pain sensitivity effect peeking between 2 and 4 h and lasting over 6 h. The study provides evidence that phytochemical extracts of the Cannabis plant, even with relatively low levels of THC, can significantly improve mechanical pressure pain in animals with established chronic neuropathic hypersensitivity.
We thank Steven Moore for his outstanding contributions to the overall vitality of the hemp used in the current study.
CBD: Benefits, Types, & Side Effects
CBD, or cannabidiol, is recommended for everything from anxiety and stress to indigestion and depression. And, a lot of people are using it. A recent Gallup poll found 1 in 7 adults in the U.S. has used CBD.
So, does it help? Studies of CBD are ongoing, but some benefits have been found.
What is CBD?
There are two types of cannabis sativa: hemp and marijuana. The hemp plant is the source of CBD used in most products.
Hemp and marijuana plants
CBD is one of a group of substances called cannabinoids derived from the cannabis sativa plant.
There are dozens of cannabinoids, as well as other substances, in cannabis sativa.
CBD is the primary cannabinoid in hemp. It has various healing properties. For example, it seems to lessen inflammation, the body’s response to illness or injury. In this way, it may help treat many different diseases.
CBD is not psychoactive; it does not have a mind-altering effect.
CBD vs. THC
Marijuana contains more THC than CBD. Hemp has a very small amount of THC, less than 0.3 percent, and not enough to cause a high. As of 2018, CBD from hemp became legal in the U.S. with the Food and Drug Administration (FDA) maintaining control.
CBD’s main property is healing and it’s derived from the hemp plant. On the other hand, THC’s main property is mind-altering and it’s derived from the marijuana plant.
Excessive and continued use of CBD may lead to side effects, including memory loss, slow reaction time, and changes in mood such as irritability.
How CBD Works
As stated above, CBD is in a class of chemicals called cannabinoids. Because it comes from a plant, it is further classified as a phytocannabinoid.
The human body also produces natural cannabinoids, called endocannabinoids.
Both variations of cannabinoids act on cannabinoid receptors. These receptors are part of the complex endocannabinoid system (ECS). The system regulates the release of neurotransmitters (chemicals that communicate between nerve cells) in the brain, as well as in other parts of the nervous system. The ECS responds to both types of cannabinoids, phyto- and endo-.
By acting on the ECS, CBD may have many different effects on the body. Examples include: balancing the body’s overall physical functions (homeostasis), reducing pain sensation, and lessening the body’s reaction to injury or inflammation.
Medical Uses of CBD
Studies are ongoing, but some results show that CBD may be effective in reducing anxiety/stress and chronic (long-term) pain like back pain. It may also be effective for insomnia, or trouble sleeping.
There are studies of oral, topical, and inhaled CBD products for use in many other conditions, including dystonia (movement disorder), Fragile X syndrome (rare genetic disorder), graft-versus-host disease (bone marrow transplant rejection), multiple sclerosis (MS), opioid withdrawal, schizophrenia, and smoking cessation. CBD is also used to alleviate symptoms associated with Parkinson’s disease, but some study results advise against it.
Types of CBD Products
CBD oil may be used both ways.
Other oral products include edible gummies and capsules. Topical CBD products may also be found in lotions, creams, or balms. Again, they are available in various concentrations.
CBD should be used according to the manufacturer’s instructions. Make sure you read and follow the label carefully. Only use the amount instructed. Using more may increase the chance of side effects, interactions, or other problems.
The dose of a CBD product depends on the form and strength, as well as the concentration of CBD in it. It’s also based on whether or not it has other active ingredients.
Side Effects of CBD
The most common side effects are tiredness or drowsiness and diarrhea. Other side effects are dry mouth, vomiting, decreased appetite, weight loss, and abnormal liver function blood tests.
CAUTION: Since CBD may cause tiredness or drowsiness, be very careful when driving, using tools or other equipment, or performing other activities involving risks.
CBD and Medical Conditions
(name=interactions)CAUTION: CBD should not be taken by people with liver disease or Parkinson's disease.
CBD and Medicines/Drugs
CAUTION: CBD should not be used with medicines that are prescribed to control seizures or epilepsy.
There are also other medicines you should not take with CBD. Doing so may increase the effects of those medicines. As an example, taking CBD with drugs that cause drowsiness may cause the person to become even more sleepy.
CBD may also increase side effect risks if certain medicines are used together. There may be interactions with some commonly prescribed drugs, including warfarin, lithium, sertraline, tramadol, codeine, valproic acid, carbamazepine, and captopril. To avoid interactions, speak to your doctor or pharmacist before taking CBD with other medications.
CBD, Foods, and Herbs
CAUTION: Fatty foods may increase how CBD is absorbed by the body.
CAUTION: Taking CBD with other herbs that cause drowsiness or sleepiness may increase this effect.
Oral CBD for Pain
The National Academies of Sciences (NAS) found significant evidence that cannabis was an effective treatment for long-term (chronic) pain. However, much of the research was done outside of the U.S. And the forms of cannabis studied in the U.S. were not the same as those commonly used.
Reviews and meta-analyses of cannabinoids found the following:
Studies looked at the use of cannabinoids (THC alone and CBD combined with THC) in people with chronic pain. In general, results showed improvements in pain measures, but they were not statistically significant.
Studies found evidence, although not high-quality, that cannabis-based medicines reduced long-term nerve (chronic neuropathic) pain. All but two studies used plant-based THC/CBD mouth spray products (the other two used synthetic oral THC products).
Results of observational studies and randomized controlled trials (RCTs) of the effectiveness of cannabinoids in chronic non-cancer pain showed a 30% reduction in pain in 1 out of 3 of those using cannabinoids. These results were considered significant.
Topical CBD for Pain
There is also continuing research on the safety and effectiveness of topical CBD. Some of the research includes the following:
Although not in humans, an animal study found transdermal CBD had the ability to lessen the pain and inflammation of arthritis.
Topical cannabidiol oil was studied in 29 people with lower limb peripheral neuropathy. After using the oil for 4 weeks, results showed less intense and sharp pain and fewer other uncomfortable sensations.
Applications of transdermal cannabidiol were studied in people with temporomandibular (joint of the jaw) disorders (TMD) that caused myofascial (coverings of muscle) pain. Those studied had less muscle tension and pain after applying the topical CBD for 2 weeks.
Oral CBD to Help with Sleep
Oral CBD products may be used to help with sleep. This research includes the following:
Early results of research suggest that a 160mg dose of cannabidiol before bed significantly improves sleep duration compared to a placebo in patients with insomnia. Smaller doses did not have this effect. Also, patients did not feel drowsy the next morning.
Early research on CBD for the treatment of insomnia suggests that it may be effective. Additional studies are needed.
Animal studies of CBD found increased total sleep and improved sleep quality when sleep issues were associated with anxiety/stress.
Medical cannabis users reported they used cannabis with higher CBD and lower THC concentrations for their insomnia. They also reported a decrease in the time required to fall asleep.
A review and meta-analysis of 8 studies with low-quality evidence of cannabis-based medicines found that they were better at reducing sleep problems compared to inactive medicines (placebo).
A review of clinical trials of the effect of cannabinoids on sleep suggested that cannabinoids could improve sleep quality, decrease sleep disturbances, and decrease the time it takes to fall asleep. However, there were limiting factors, such as the small size of the studies.
An app was used to measure changes in insomnia in over 400 people taking medical cannabis. Results showed an average symptom severity reduction of 4.5 points on a 10-point scale, a significant improvement in insomnia.
Another review with meta-analysis of 104 studies evaluated cannabinoids for the treatment of chronic non-cancer pain. Within this review and analysis, the effect of cannabinoids on sleep was also examined. There was low-quality evidence of improved sleep.
Because it is so widely available and recommended for so many problems, it must be used carefully and purchased from reliable sources.
CBD is just one of many supplements that can alleviate back pain or insomnia. Take a Goodpath assessment for an integrative program that incorporates supplements, nutrition, mind-body therapies, and exercise.