Sex differences of THC-induced effects
description
Transcript of Sex differences of THC-induced effects
![Page 1: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/1.jpg)
Sex differences of THC effects in humans
Linda Klumpers
Clinical scientist
![Page 2: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/2.jpg)
Background
THC study
7 ♀ drop-outs (out of 11) vs 1 ♂ (out of 11): coincidence?
Adipose tissue composition Metabolism Hormones
![Page 3: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/3.jpg)
Gaps in knowledge
Few human studies Observational studies Cannabis administration
![Page 4: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/4.jpg)
Methods - Design
Healthy ♀ (n=11) and ♂ (n=11) Mild cannabis users Mono-phasic contraceptive (♀)
Randomised, double blind, 2-way cross-over design 2, 6, 6 mg THC or placebo inhalation (90-minute
intervals)
![Page 5: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/5.jpg)
Methods - Inhalation
![Page 6: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/6.jpg)
Methods - Measurements
Pharmacokinetics (PK) Plasma samples THC, 11-OH-THC, THC-COOH
Pharmacodynamics (PD) Visual analogue scale (VAS) mood (mood,
calmness, alertness) VAS psychedelic (‘feeling high’, external and
internal perception) Neuro-endocrine (cortisol, prolactin, LH, FSH) Heart rate
Safety Adverse events (AE), heart rate, blood pressure
Analysis Linear mixed effect modelling for comparisons
![Page 7: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/7.jpg)
Demographics
Females Males
Age (years)* 22 ± 2 22 ± 3
Height (cm)* 171 ± 6 184 ± 6
Weight (kg)* 67 ± 9 76 ± 13
BMI (kg/m2)* 23.0 ± 2.6 22.4 ± 2.7
THC use (/year)** 6 (4-8) 12 (6-14)
THC total use** 19 (16-65) 31 (18-196)
*Mean ± SD
**Median (IQR)
![Page 8: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/8.jpg)
Results – Study Population
2 mg (t=0 min)
• ♂ n=11
• ♀ n=11
6 mg (t=90 min)
• ♂ n=11
• ♀ n=8
6 mg (t=180 min)
• ♂ n=10
• ♀ n=4
![Page 9: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/9.jpg)
Adverse events
AE Females Males
Mild Moderate Mild Moderate
Anxiety 1 5 0 0
Nausea 2 4 0 1
![Page 10: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/10.jpg)
PK THC
0:00 1:00 2:00 3:00 4:00 5:00 6:00
Time (hh:mm)
0
100
200
THC
Con
cent
ratio
n (n
g/m
L)
Males
Females
![Page 11: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/11.jpg)
0:00 1:00 2:00 3:00 4:00 5:00 6:00
Time (hh:mm)
0
1
2
3
4
5
6
7
8
11-O
H-T
HC
Con
cent
ratio
n (n
g/m
L)
Males
Females
PK 11-OH-THC
![Page 12: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/12.jpg)
Feeling high
0:00 1:00 2:00 3:00 4:00 5:00 6:00 7:00
Time (hh:mm)
0
1
2
Feel
ing
high
(log
(mm
))
MalesTHC
MalesPlacebo
FemalesTHC
FemalesPlacebo
*
![Page 13: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/13.jpg)
External perception
0:00 1:00 2:00 3:00 4:00 5:00 6:00 7:00
Time (hh:mm)
0
1
2
Ext
erna
l per
cept
ion
(log(
mm
))
MalesTHC
MalesPlacebo
FemalesTHC
FemalesPlacebo
![Page 14: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/14.jpg)
Anxiety
0:00 1:00 2:00 3:00 4:00 5:00 6:00 7:00
Time (hh:mm)
0
1
2
Anx
iety
(log
(mm
))
MalesTHC
MalesPlacebo
FemalesTHC
FemalesPlacebo
![Page 15: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/15.jpg)
Results
Sex differences VAS Internal perception VAS Alertness
Treatment effect, no sex differences Heart rate Cortisol
No treatment effect Prolactin FSH LH
![Page 16: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/16.jpg)
Conclusion
Females showed higher THC and 11-OH-THC concentrations
Females showed larger PD effects
![Page 17: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/17.jpg)
Discussion
Sex differences in PD effects could be caused by differences in THC and 11-OH-THC PK
Sex differences in PK could be caused by differences in
Metabolism Adipose tissue composition Hormones THC use
![Page 18: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/18.jpg)
Acknowledgements
Centre for Human Drug Research Amita Sandhu Erik T. te Beek Joop M.A. van Gerven Marieke L. de Kam
Leiden University Medical Center, Dpt Radiology Roelof P. Soeter Serge R.A.B. Rombouts
Contact: www.chdr.nl – [email protected]
![Page 19: Sex differences of THC-induced effects](https://reader036.fdocuments.in/reader036/viewer/2022062513/5565339cd8b42a767f8b5426/html5/thumbnails/19.jpg)
Questions?