Location
Philadelphia, PA
Start Date
10-5-2021 12:00 AM
Description
Statement of Purpose, Innovation or Hypothesis: The current US Food & Drug Administration (FDA) approved armamentarium for treatment of neuropathic pain (NP) includes calcium channel alpha-2-delta ligands (gabapentin, pregabalin) and a selective serotonin-norepinephrine re-uptake inhibitor (duloxetine); however, tricyclic antidepressants (amitriptyline) and antiepileptic agents (carbamazepine) have also been employed. Most have limited effectiveness and/or cause intolerable adverse reactions, leading to discontinuation. Neuropathic pain patients have also been treated with opioid analgesics, which have their own attendant risks (e.g., addiction, hyperalgesia, endocrinopathy) and limited efficacy. Delta-9-Tetrahydrocannabinol (THC) (dronabinol), C-III, is FDA-approved as an appetite stimulant and antiemetic. Doses ranging from 2.5 mg/day to 40 mg/day have been employed. As an anti-emetic, efficacy is achieved in doses of 5 mg three or four times daily. Dronabinol is not currently FDA-approved for treatment of chronic NP. Studies have found evidence supporting the analgesic effects of cannabinoids across various neuropathic disorders but many lacked scientific rigor.
Description of Methods and Materials: Inclusion Criteria: 18 to 65 years of age; diagnosis of NP of two or more months duration. Exclusion Criteria: non-English speaking; cardiovascular conditions; epilepsy or any seizure disorder; liver function problems; depression or other psychological problems as determined by a score of ≥10 on the PHQ-9 screen; substance use disorder as determined by a score of ≥18 on the SOAPP-R; taking antidepressants for less than 8 wks antipsychotics, Alzheimer's Disease medications or CNS stimulants. From referring physicians, a request was made for all lab results taken within one year prior to recruitment including serum blood urea nitrogen, serum creatinine and Liver function Tests. A urine drug screening (UDS) including MS/GC confirmation of any positive results was performed. Any discrepancy between positive UDS data and information given by the patient resulted in termination from the investigation. Patients were seen weekly with vital signs taken. Each day, the study patient completed a 0–10 pain diary three times daily. In addition, they recorded how much of their pain medications they took that day. Weeks One and Two: establish each patient's baseline pain scores and analgesic usage. Week 3: up-titration process initiated; 5 mg THC orally at bedtime. Weeks Four to Six: dose increased 5 mg/week. Goal was 20 mg in Week 6. Any patient experiencing an undesirable adverse event was withdrawn.
Data and Results: Thus far, six patients have completed the full up-titration to 20 mg on Week 6. The average pain score dropped from 4.9 to 2.7 at end of Week 6. Of the five who were using analgesics, most were able to decrease dosages of gabapentin, carbamazepine and ibuprofen.
Interpretation, Conclusion or Significance: In this limited pilot study to date, six patients completed the four-week up-titration from daily 5 mg THC to 20 mg THC. The average reduction in pain scores was 44.9%. In addition, most patients used less gabapentin, carbamazepine and ibuprofen. Our investigation continues to the goal of studying a total of 20 patients who complete the 20 mg per day goal.
Embargo Period
3-18-2022
Analgesic Effect of Delta-9-Tetrahydrocannabinol on Patients With Chronic Neuropathic Pain During a Four-week Period: A Pilot Study
Philadelphia, PA
Statement of Purpose, Innovation or Hypothesis: The current US Food & Drug Administration (FDA) approved armamentarium for treatment of neuropathic pain (NP) includes calcium channel alpha-2-delta ligands (gabapentin, pregabalin) and a selective serotonin-norepinephrine re-uptake inhibitor (duloxetine); however, tricyclic antidepressants (amitriptyline) and antiepileptic agents (carbamazepine) have also been employed. Most have limited effectiveness and/or cause intolerable adverse reactions, leading to discontinuation. Neuropathic pain patients have also been treated with opioid analgesics, which have their own attendant risks (e.g., addiction, hyperalgesia, endocrinopathy) and limited efficacy. Delta-9-Tetrahydrocannabinol (THC) (dronabinol), C-III, is FDA-approved as an appetite stimulant and antiemetic. Doses ranging from 2.5 mg/day to 40 mg/day have been employed. As an anti-emetic, efficacy is achieved in doses of 5 mg three or four times daily. Dronabinol is not currently FDA-approved for treatment of chronic NP. Studies have found evidence supporting the analgesic effects of cannabinoids across various neuropathic disorders but many lacked scientific rigor.
Description of Methods and Materials: Inclusion Criteria: 18 to 65 years of age; diagnosis of NP of two or more months duration. Exclusion Criteria: non-English speaking; cardiovascular conditions; epilepsy or any seizure disorder; liver function problems; depression or other psychological problems as determined by a score of ≥10 on the PHQ-9 screen; substance use disorder as determined by a score of ≥18 on the SOAPP-R; taking antidepressants for less than 8 wks antipsychotics, Alzheimer's Disease medications or CNS stimulants. From referring physicians, a request was made for all lab results taken within one year prior to recruitment including serum blood urea nitrogen, serum creatinine and Liver function Tests. A urine drug screening (UDS) including MS/GC confirmation of any positive results was performed. Any discrepancy between positive UDS data and information given by the patient resulted in termination from the investigation. Patients were seen weekly with vital signs taken. Each day, the study patient completed a 0–10 pain diary three times daily. In addition, they recorded how much of their pain medications they took that day. Weeks One and Two: establish each patient's baseline pain scores and analgesic usage. Week 3: up-titration process initiated; 5 mg THC orally at bedtime. Weeks Four to Six: dose increased 5 mg/week. Goal was 20 mg in Week 6. Any patient experiencing an undesirable adverse event was withdrawn.
Data and Results: Thus far, six patients have completed the full up-titration to 20 mg on Week 6. The average pain score dropped from 4.9 to 2.7 at end of Week 6. Of the five who were using analgesics, most were able to decrease dosages of gabapentin, carbamazepine and ibuprofen.
Interpretation, Conclusion or Significance: In this limited pilot study to date, six patients completed the four-week up-titration from daily 5 mg THC to 20 mg THC. The average reduction in pain scores was 44.9%. In addition, most patients used less gabapentin, carbamazepine and ibuprofen. Our investigation continues to the goal of studying a total of 20 patients who complete the 20 mg per day goal.