CBD Oil And Gabapentin

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Clinical studies have shown that the major psychoactive ingredient of Cannabis sativa Δ9-tetrahydrocannabinol (THC) has some analgesic efficacy in neuropathic pain states. However, THC has a significant side effect profile. We examined whether the profile of THC could be improved by co-administering … There is no interaction between CBD oil and gabapentin. However, both may cause sedative effects, which can be additive if used together. Patients with neuropathic pain may benefit from treatment with cannabis-based medicines or medical cannabis (CBM/MC), particularly in terms of reduced use of gabapentin and fewer days admitted to hospitals, compared with propensity score matched controls. CBM/MC did not, however, reduce the use of o …

THC and gabapentin interactions in a mouse neuropathic pain model

Clinical studies have shown that the major psychoactive ingredient of Cannabis sativa Δ9-tetrahydrocannabinol (THC) has some analgesic efficacy in neuropathic pain states. However, THC has a significant side effect profile. We examined whether the profile of THC could be improved by co-administering it with the first-line neuropathic pain medication gabapentin. This was done using the chronic constriction injury (CCI) model of neuropathic pain in C57BL6 mice. At 8 days post-CCI nerve injury, acute systemic administration of gabapentin produced a dose-dependent decrease in CCI-induced mechanical and cold allodynia, and increased motor incoordination. Coadministration of THC and gabapentin in a fixed-ratio dose-dependently reduced mechanical and cold allodynia, and produced all the side-effects observed for THC, including motor incoordination, catalepsy and sedation. Isobolographic analysis indicated that the ED50 for the THC:gabapentin induced reduction in allodynia was 1.7 times less than that predicted for an additive interaction. The therapeutic window of combination THC:gabapentin was greater than that for THC alone. These findings indicate that gabapentin synergistically enhances the anti-allodynic actions of THC and improves its therapeutic window. Thus, THC may represent a potential adjuvant for neuropathic pain medications such as gabapentin.

Keywords: Cannabinoid; Gabapentin; Isobolograph; Neuropathic pain; Synergy; Tetrahydrocannabinol.

Copyright © 2018 Elsevier Ltd. All rights reserved.

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Cited by

Brings VE, Payne MA, Gereau RW 4th. Brings VE, et al. Pain Rep. 2022 Aug 25;7(5):e1035. doi: 10.1097/PR9.0000000000001035. eCollection 2022 Sep-Oct. Pain Rep. 2022. PMID: 36034600 Free PMC article.

Casey SL, Mitchell VA, Sokolaj EE, Winters BL, Vaughan CW. Casey SL, et al. Int J Mol Sci. 2022 Aug 3;23(15):8649. doi: 10.3390/ijms23158649. Int J Mol Sci. 2022. PMID: 35955774 Free PMC article.

Bukke VN, Archana M, Villani R, Serviddio G, Cassano T. Bukke VN, et al. Pharmaceuticals (Basel). 2021 Sep 24;14(10):965. doi: 10.3390/ph14100965. Pharmaceuticals (Basel). 2021. PMID: 34681189 Free PMC article. Review.

Brito BE, García MA, De Gouveia YM, Bolaños P, Devis S, Bernal G, Tortorici-Brito VA, Baute L, Díaz-Serrano G, Tortorici V. Brito BE, et al. Int J Mol Sci. 2021 Sep 7;22(18):9671. doi: 10.3390/ijms22189671. Int J Mol Sci. 2021. PMID: 34575835 Free PMC article.

Serrano Afonso A, Carnaval T, Videla Cés S. Serrano Afonso A, et al. J Clin Med. 2021 Aug 11;10(16):3533. doi: 10.3390/jcm10163533. J Clin Med. 2021. PMID: 34441829 Free PMC article. Review.

Neurontin (Gabapentin) With CBD Oil Interaction

In our latest question and answer, the pharmacist discusses the potential interaction between CBD oil and gabapentin.

Sue asked

I have pretty bad neuropathy and have been prescribed gabapentin. Is it safe to also use CBD oil?

Answer

Neurontin (gabapentin) is not known to interact with CBD (cannabidiol) oil. However, there is a lack of data available overall when it comes to potential drug interactions with CBD as it is not well studied (currently at least) in that regard.

Nevertheless, based on what we know about CBD and gabapentin metabolism, an interaction appears to be unlikely, as will be discussed below.

What Is CBD?

Cannabidiol (CBD) is one of the many constituents of the cannabis (i.e. marijuana) plant. In fact, depending on the specific strain of cannabis, CBD can make up over 40% of the total constituents (1).

An interesting characteristic of CBD is that it is ‘non-psychoactive’, meaning it doesn’t cause a “high” or euphoria (2). This is distinct from THC (tetrahydrocannabinol), which is largely responsible for the high that is associated with marijuana.

Multiple studies have shown CBD to be safe for most individuals and has an extremely wide dosage range. Doses ranging from a few milligrams all the way up to 1,500 mg have been taken with few adverse effects for up to four weeks (3).

CBD has numerous effects on the body, many of which aren’t fully understood. Nevertheless, CBD has been used for several indications, including:

  • Bipolar disorder (4)
  • Dystonia (5)
  • Epilepsy (6)
  • Huntington’s Disease (7)
  • Multiple Sclerosis (8)
  • Parkinson’s Disease (9)
  • Schizophrenia (10)
  • Anxiety (11)
  • Neuropathy (19)
  • Inflammation (20)
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CBD certainly looks promising from a medical standpoint, but more studies are needed to determine its effects and overall efficacy.

As CBD may help with various types of pain (e.g. neuropathy), it makes sense to look into its use for those indications and whether or not it is safe with other medications for those indications (like gabapentin).

CBD Drug Interactions

When it comes to drug interactions, many aren’t definitively known but there are some theoretical ones that are proposed based on how CBD is metabolized.

CBD is metabolized by the cytochrome P450 system, the major enzymes involved in drug metabolism. Most drug interactions involve this system of enzymes. When a drug metabolizing enzyme is inhibited, concentrations of a drug may be increased due to decreased metabolism. For example:

  • Drug A is metabolized by CYP 3A4.
  • Drug B inhibits CYP 3A4.
  • Taking Drug B with Drug A may result in increased concentrations of Drug A (due to decreased metabolism). This can potentially increase the risk of side effects.

Studies have shown that CBD can affect numerous enzymes, which could potentially affect how other drugs are metabolized.

Studies have shown that CBD can potentially inhibit:

We say potentially inhibit since lab studies have shown that CBD can inhibit the above enzymes, but several human studies don’t show consistent results.

There is a prescription CBD product known as Epidiolex that offers a little insight unfortunately into potential interactions. It has very few details on specific interactions, and the prescribing information for the drug only theorizes potential interactions based on the potential for CYP metabolizing enzyme inhibition (16). The only drugs it mentions that have confirmed drug interactions are:

  • Diazepam (increases concentrations)
  • Onfi (Clobazam) (increases concentrations)

How Is Gabapentin Metabolized?

The vast majority of drugs are metabolized via the CYP enzyme system. Gabapentin, however, is not. Interestingly, it is not metabolized to any appreciable degree in humans and is excreted intact in the urine (17).

Due to the lack of gabapentin metabolism, CBD isn’t thought to interact with it and should not affect levels of gabapentin in the body if taken at the same time.

The only thing to be aware of is that high doses of CBD can have sedative and slight hypnotic effects (18). Due to this, it is a general warning that CBD be used cautiously with CNS (central nervous system) depressants, like gabapentin, due to the risk of additive sedation.

Cannabis-based medicines and medical cannabis for patients with neuropathic pain and other pain disorders: Nationwide register-based pharmacoepidemiologic comparison with propensity score matched controls

Background: Neuropathic pain and other pain disorders have received attention as potential indications for use of cannabis-based medicines or medical cannabis (CBM/MC). Evidence regarding the efficacy and safety of CBM/MC for pain disorders is, however, insufficient. Denmark introduced a pilot programme of medical cannabis in January 2018. We aimed to evaluate efficacy, safety, and non-specific effects of CBM/MC used under the pilot programme compared with controls.

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Methods: We conducted a nationwide register-based cohort study in Denmark, identifying all individuals redeeming at least one prescription for CBM/MC for either neuropathic pain (n = 1817) or other and unspecified pain disorders (n = 924), and to match one control to each case using propensity score matching.

Results: Among both patient groups, users of THC used more opioids during follow-up than controls. Among patients with neuropathic pain, however, users of either CBD, THC, or combined CBD + THC used less gabapentin than controls. Users of all three classes of CBM/MC were hospitalized fewer days than controls among neuropathic-pain patients but not among patients with other or unspecified pain disorders.

Conclusions: CBM/MC were generally safe and even displayed some positive effects among patients with neuropathic pain. We conclude that CBM/MC are safe and possibly efficacious for patients with neuropathic pain but not patients with other pain disorders.

Significance: Patients with neuropathic pain may benefit from treatment with cannabis-based medicines or medical cannabis (CBM/MC), particularly in terms of reduced use of gabapentin and fewer days admitted to hospitals, compared with propensity score matched controls. CBM/MC did not, however, reduce the use of opioids. We did not find evidence that CBM/MC were effective for patients with other pain disorders.

© 2021 European Pain Federation – EFIC®.

Comment in

Häuser W, Fitzcharles MA. Häuser W, et al. Eur J Pain. 2022 Jan;26(1):3-4. doi: 10.1002/ejp.1881. Epub 2021 Nov 11. Eur J Pain. 2022. PMID: 34743399 No abstract available.

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Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W. Mücke M, et al. Cochrane Database Syst Rev. 2018 Mar 7;3(3):CD012182. doi: 10.1002/14651858.CD012182.pub2. Cochrane Database Syst Rev. 2018. PMID: 29513392 Free PMC article. Review.

Kudahl B, Berg ME, Posselt CM, Nordentoft M, Hjorthøj C. Kudahl B, et al. Complement Ther Clin Pract. 2021 Nov;45:101476. doi: 10.1016/j.ctcp.2021.101476. Epub 2021 Aug 20. Complement Ther Clin Pract. 2021. PMID: 34425501

Petzke F, Tölle T, Fitzcharles MA, Häuser W. Petzke F, et al. CNS Drugs. 2022 Jan;36(1):31-44. doi: 10.1007/s40263-021-00879-w. Epub 2021 Nov 21. CNS Drugs. 2022. PMID: 34802112 Free PMC article. Review.

Häuser W, Fitzcharles MA. Häuser W, et al. Eur J Pain. 2022 Jan;26(1):3-4. doi: 10.1002/ejp.1881. Epub 2021 Nov 11. Eur J Pain. 2022. PMID: 34743399 No abstract available.

[No authors listed] [No authors listed] Drugs R D. 2003;4(5):306-9. doi: 10.2165/00126839-200304050-00005. Drugs R D. 2003. PMID: 12952500 Review.

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