Sex differences of THC effects in humans

Linda Klumpers

Clinical scientist

Background

THC study

7 ♀ drop-outs (out of 11) vs 1 ♂ (out of 11): coincidence?

Adipose tissue composition Metabolism Hormones

Gaps in knowledge

Few human studies Observational studies Cannabis administration

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)

Methods - Inhalation

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

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)

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

Adverse events

AE Females Males

Mild Moderate Mild Moderate

Anxiety 1 5 0 0

Nausea 2 4 0 1

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

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

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

*

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

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

Results

Sex differences VAS Internal perception VAS Alertness

Treatment effect, no sex differences Heart rate Cortisol

No treatment effect Prolactin FSH LH

Conclusion

Females showed higher THC and 11-OH-THC concentrations

Females showed larger PD effects

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

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 – lklumpers@chdr.nl

Questions?