MEDICAL HEMP ( marijuana study )

INTRODUCTION

• Widesprmad use of smoked marijuana in patlents with symptomatic HIV infection in San Francisco prompted this safety study.
  
• Cannabinoid use could potentially alter HIV RNA levels by:
  
  • immune modulation via the CB2 receptor, or
    
  • cannabinoid:protease inhititor (PI) interactions via cytochrome p450.
    
• The objective of this study is to determine the safety/toxicity profile of cannabinoids in persons with HIV disease.
  
• Does metabolic interaction between cannabinoids and PI or cannabinoids and the immune system alter HIV RNA after 2l days' exposure.
  
• Is there a different metabolic interaction between PIs and cannabinoids whether orally or inhaled.
  
• What are the short-term cannabinoid effects on endocrine function, appetite, energy intake and expenditure, body weight and composition.

METHODS

• Randomized, parlially blinded, placebo controlled, 21 day inpatient study.
  
• General Clinical Research Center admission consisted of 4 lead in days and 21 study treatment days.
  
• Ftrst patient enrolled on May 12 1999; last completed on May 28, 2000.
  
• Sixty-seven (67) patients were randomized to smoke marijuana (3.95% THC), take oral dronabinol, or take an oral placebo, 3 times daily before meals.
  
• Sixty-two (62),patients completed the 21 day study period.
  
• HIV RNA levels measured usng bDNA version 3.0 ten times during the study.

INCLUSION CRITERIA

• HIV-positve
  
• Stable anti-retroviral regimen containing indinavir or nelfinavir
  
• Stable HIV RNA viral load
  
• Prior use (>6 times) of marijuana

EXCLUSION CRITERIA

• Use of marijuana within 30 days of enrollment
  
• Active substance use including tobacco
  
• Wasting (>10% weight loss in the past 6 months)
  
• Active opportunistic infections or malignancies requiring acute treatment

PATIENT CHARACTERISTICS

• Demographics (N=67)

• Gender
  
  Male 60 (90%)
  Female 3 (4%)
  Male to Female Transgender 4 (6%)
  

• Age
  
  <40 22 (33%)
  40-49 33 (49%)
  50+ 12 (18%)
  (Median; 43; Range; 26-80)

• Ethnicity
  
  White 32 (48%)
  African American / Black 13 (19%)
  Latino 11 (16%)
  Asian / Pacific Islander 2 (3%)
  Mixed / Other 9 (13%)

Clinical Characteristics (N=67)

• Prior Opportunistic Infection
  
  Yes 33 (49%)
  No 34 (51%)

• Baseline CD4 Count (2 missing)
  
  < 200 18 (28%)
  200-499 34 (52%)
  >500 13 (20%)
  (Median: 300; Range; 9-844)

• Baseline Viral load (copies / ml)
  
  <50 37 (55%)
  50-499 10 (16%)
  500-9999 13 (19%)
  >10,000 7 (10%)

• Baseline Weight (kg)
  
  <70 14 (23%)
  70-79 19 (31%)
  80-89 14 (23%)
  >90 15 (24%)
  (Median: 79; Range; 44-153)

Randomization by Protease Inhibitor and Study Arm (N =67)

Protease Inhibitor Indivanir Nelfinavir Total

Marijuana 9 (13%) 12 (18%) 21 (31%)

Dronabinal 12 (18%) 13 (19%) 25 (37%)

Placebo 9 (13%) 12 (18%) 21 (31%)

Total 30 (45%) 37 (55%) 67

There were no statistically significant differences in patient demographic or clinical characteristics by study arm

RESULTS

• Viral Load Change by Arm
  

• Mean Change in Log10 Viral Load by Arm
  Repeated Measures Model (N=62)
  

• Change in Mean Log10 Viral Load by Arm
  Illustration of Model (N =62)
  

Repeated measures model adjusted for protease
inhibitor, baseline viral load, and baseline CD4.

• Caloric Intake and Weight Gain (N=62)
  

• Success of Blinding in Oral Arm (N=42)

• Dronabinol recipients
  
  Thought dronabinol 17
  Thought placebo 4
  Uncertain/changed 1

• Placebo recipients
  
  Thought placebo 9
  Thought dronabinol 9
  Uncertain/changed 2

• Correlation - 26/42 (62%)

• Adverse Events (N =67)

• Marijuana Arm
  
  Grade 2 - Neuropsychiatric symtoms. Patient chose to leave study.
  Grade 2 - Tachycardia. Patent remained on study drug.
  Grade 3 - Neuropychiatric symtoms. Patient treated with Ativan; remained on study drug.

• Dronabinol Arm
  
  Grade 2 - Neuropsychiatric symtoms. Patient chose to leave study.
  Grade 2 - Headache and nausea. Patient chose to leave study.
  Grade 3 - Left flank pain possibly related to Crixivan, not related to study drug. Patient remained on study drug.
  Grade 5 - Death occurred 58 days after completing study; judged to be unrelated to study drug (cause of death GI bleed secondary to portal hypertension)

• Placebo Arm
  
  - No adverse events reported.

SUMMARY

• Cannabinoids, smoking and oral, do not adversely effect HIV RNA levels after 21 days exposure.
  
• Smoked marijuana and dronabinol lead to significant increases in caloric intake and weight.
  
• Future trials should investigate the effectiveness of marijuana in:
  
  • Appetite stimulation / Weight gain
    
  • Nausea
    
  • Pain
    

COLLABORATIONS

• VIROLOGY - Tarek Elbeik
  
• PHARMACOLOGY - Fran Aweeka - Neal Benowitz
  
• ENDOCRIN / METABOLIC - Kathleen Mulligan - Morris Schambelan - Doris Dare
  
• IMMUNOGY - Barry Bredt - Mika McCune
  
• BIOSTATISTICS - Joan Hiton - Starley Shade
  
• COMMUNITY CONSORTIUM - Carroll Child - Roz Leiser - Tom Mitchell - Tiffany Sommer
  
• CLINICAL ASSESSMENTS - Judith Aberg - Steven Deeks

Supported by NIH grant DA/MH11607. Dronabinol and placebo provided by Roxane Laboratories

THC Study Data for Michael

Below is some information about your individual test results while you participated in the THC study. Please bear in mind that laboratory tests were perfomed in research laboratories and are not intended to be used for clinical purposes. We encourage you to share this information with your health care provider. If you or your provider have any questions please feel free to contact us.

Dates enrolled in study: 6/4/99-6/29/99

Your randomly assigned study treatment was marinol

Viral Load:

During your stay in the GCRC your viral load was drawn ten times. The first two results were obtained before you started your study treatment. This graph represents your viral load results during the time you were in the GCRC and on your two follow up visits (if you attended them). If no line appears on this graph your viral load was undetectable (<50) during the entire study.

CD4 (T-cell):

Your CD4 count was measured five times in the GCRC and once at the three week follow up. This graph represents your CD4 results.

Testosterone Average:

Your testosterone level was drawn four times while you were in the study. The average of these four values was 46O. The normal range for testosterone levels in the SFGH Clinical Laboratories is 270-1194 for men and 11-83 for women.

Weight:

When you entered the GCRC, you weighed 152 lbs. When you were discharged from the study, your weight was 155 lbs. This graph shows your weight over the time you spent in the GCRC.

Percentage Body Fat:

This graph shows your percentage of body fat during the time you were in the GCRC. If no graph appears here data was not available.

Caloric Intake:

This graph represents the amount of calories you took in each day while in the GCRC.