Use of cannabinoids in treating anti-depressant-induced female sexual dysfunction

Abstract

The invention relates to compositions and methods containing hemp and/or cannabis-derived cannabidiol (CBD) for topical use in treating female sexual dysfunction induced by antidepressants, including, e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin/norepinephrine reuptake inhibitors (SNRIs), and other anti-depressants.

1 - 30 . (canceled) 
     
     
         31 . A method of ameliorating female sexual dysfunction induced by one or more antidepressants previously administered to a female subject, the method comprising:
 (a) administering a PDE-5 inhibitor, and   (b) administering a topical composition consisting essentially of CBD (“CBD-containing composition”), said composition being applied by the subject to the mucosal surface of the subject's genital arousal area(s) prior to a sexual activity,   
       thereby ameliorating the subject's sexual dysfunction. 
     
     
         32 . The method of claim  331 , wherein the female subject is a human who has been diagnosed with one or more disorders or conditions treated by taking an anti-depressant, selected from the group consisting of major depressive disorder (MDD), persistent depressive disorder (dysthymia), melancholic depression. 
     
     
         33 . The method of claim  331 , wherein the female subject is a human and has been diagnosed with one or more disorders or conditions treated by taking an anti-depressant, selected from the group consisting of generalized anxiety disorder (GAD), social anxiety disorder (SAD), attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), bulimia nervosa (bulimia), panic disorder, and post-traumatic stress disorder (PTSD). 
     
     
         34 . The method of claim  331 , wherein the female subject is a human and has been diagnosed with one or more disorders or conditions treated by taking an anti-depressant, selected from the group consisting of premenstrual dysphoric disorder, menopause-associated vasomotor symptoms, fibromyalgia, neuropathic pain, diabetic peripheral neuropathy (DPN), and chemotherapy-induced neuropathy. 
     
     
         35 . The method of claim  331 , wherein the antidepressant causing sexual dysfunction is selected from an SSRI, an SNRI, a tricyclic antidepressant, and a tetracyclic anti-depressant. 
     
     
         36 . The method of claim  335 , wherein a) the SSRI is selected from sertraline, citalopram, fluoxetine, escitalopram, paroxetine, fluvoxamine, duloxetine, venlafaxine, and desvenlafaxine; b) the SNRI is selected from duloxetine, venlafaxine, desvenlafaxine, milnacipran, and levomilnacipran; c) the tricyclic antidepressant is selected from clomipramine, trimipramine, amitriptyline, desipramine, imipramine, lofepramine, doxepin, nortriptyline, amoxapine, and protriptyline; and/or the tetracyclic antidepressant is selected from maprotiline and mirtazapine. 
     
     
         37 . The method of  claim 31 , wherein said topical composition is formulated as a lotion, an ointment, a cream, a suspension, a paste, a gel, a balm, a tincture, an emulsion, or a serum, any one of which is applied to the female genitalia. 
     
     
         38 . The method of  claim 31 , wherein the genital arousal area includes genitalia with absorptive mucosa, comprising one or more of: the introitus, the vulva, the labia minora, the clitoris and the vaginal vault. 
     
     
         39 . The method of claim  331 , wherein the phosphodiesterase type 5 (PDE-5) inhibitor is selected from sildenafil, tadalafil, vardenafil, avanafil, and udenafil. 
     
     
         40 . The method of claim  331 , wherein the PDE-5 inhibitor is added to the CBD-containing composition. 
     
     
         41 . The method of claim  331 , wherein the PDE-5 inhibitor is administrated topically separately from the CBD-containing composition before, concurrently, or after the application of the CBD-containing composition. 
     
     
         42 . The method of claim  331 , wherein the PDE-5 inhibitor is administrated orally before, concurrently, or after the application of the CBD-containing composition. 
     
     
         43 . The method of claim  331 , wherein the female sexual dysfunction is characterized by one or more of the following characteristics: difficulty achieving arousal and/or insufficient lubrication, difficulty in achieving and maintaining engorgement, and difficulty in achieving and maintaining lubrication. 
     
     
         44 . The method of claim  331 , wherein the female sexual dysfunction is characterized by one or more of the following characteristics: difficulty in achieving orgasm, low orgasm intensity, or anorgasmia. 
     
     
         45 . The method of claim  331 , wherein the female subject was previously treated with an anti-depressant that induced sexual dysfunction and the subject has persistent sexual dysfunction despite discontinuation of the antidepressant therapy. 
     
     
         46 . The method of claim  331 , wherein the female subject is premenopausal. 
     
     
         47 . The method of claim  331 , wherein the female subject is post-menopausal. 
     
     
         48 . The method as in claim  331 , wherein the subject has been previously treated with, but did not satisfactorily respond to, one or more of the following treatments: (1) change of the time the antidepressant medication is taken, (2) drug holidays, (3) decrease the dose of the medication, (4) switching to or addition of mirtazapine, (5) switching to or addition of bupropion, (6) topical testosterone, (7) amantadine, (8) switching to or addition of trazodone, (9) methylphenidate, (10) behavioral therapy, and (11) acupuncture. 
     
     
         49 . The method as in claim  331 , wherein the female subject is further treated with one or more of the following treatments: (1) change of the time the antidepressant medication is taken, (2) drug holidays, (3) decrease the dose of the medication, (4) switching to or addition of mirtazapine, (5) switching to or addition of bupropion, (6) topical testosterone, (7) acupuncture, (8) amantadine, (9) switching to or addition of trazodone, (10) methylphenidate, (11) behavioral therapy, and (12) dietary supplements. 
     
     
         50 . The method of claim  331 , wherein the amelioration of the sexual dysfunction is exhibited by one or both of the following parameters:
 i) clitoral smooth muscle relaxation; and   ii) increased vaginal and clitoral blood flow.   
     
     
         51 . The method of claim  331 , wherein the amelioration of the sexual dysfunction is exhibited by one or more of the following subjectively self-reported outcomes including:
 i) “increased lubrication/wetness during sexual activity”;   ii) “reaching orgasm more often”;   iii) “greater ease or achieving orgasm”;   iv) “being more satisfied”;   v) “higher level of sexual desire”; and   vi) “reduction in pain during sexual activity”.   
     
     
         52 . The method of claim  331 , wherein the total amount of CBD applied is from 5 mg to 1,000 mg of CBD. 
     
     
         53 . The method of claim  331 , wherein the composition is applied 1-60 min prior to sexual activity. 
     
     
         54 . The method of claim  331 , wherein the CBD-containing composition is applied at 5-30 mins prior to the sexual activity. 
     
     
         55 . The method of claim  331 , wherein CBD is hemp-derived and/or contains less than 0.3% THC by weight. 
     
     
         56 . The method of claim  331 , wherein the concentration of CBD in the composition is from 1 mg/mL to 40 mg/mL. 
     
     
         57 . The method of claim  331 , wherein the subject, upon having been treated with the CBD-containing composition for 3-6 months, reports arousal and or orgasmic improvements as measured by FSFI, wherein the improvement in sexual interest/arousal domain is by 1-2 points, and by 1-2 points in the orgasm domain of the FSFI. 
     
     
         58 . The method of claim  331 , wherein off-set time following the application of the CBD-containing composition is 0.5-5 hrs. 
     
     
         59 . A method of ameliorating female sexual dysfunction induced by one or more antidepressants previously administered to a female subject, the method comprising:
 (c) administering a smooth muscle relaxant, and   (d) administering a topical composition consisting essentially of CBD (“CBD-containing composition”), said composition being applied by the subject to the mucosal surface of the subject's genital arousal area(s) prior to a sexual activity,   
       thereby ameliorating the subject's sexual dysfunction. 
     
     
         60 . The method of  claim 58 , wherein the smooth muscle relaxant is added to the CBD-containing composition. 
     
     
         61 . The method as in  claim 59 , the smooth muscle relaxant is prostaglandin E1, papaverine, or minoxidil. 
     
     
         62 . The method of  claim 59 , wherein the female subject is a human who has been diagnosed with one or more disorders or conditions treated by taking an anti-depressant, selected from the group consisting of major depressive disorder (MDD), persistent depressive disorder (dysthymia), melancholic depression. 
     
     
         63 . The method of  claim 59 , wherein the female subject is a human who has been diagnosed with one or more disorders or conditions treated by taking an anti-depressant, selected from the group consisting of generalized anxiety disorder (GAD), social anxiety disorder (SAD), attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), bulimia nervosa (bulimia), panic disorder, and post-traumatic stress disorder (PTSD). 
     
     
         64 . The method of  claim 59 , wherein the female subject is a human who has been diagnosed with one or more disorders or conditions treated by taking an anti-depressant, selected from the group consisting of premenstrual dysphoric disorder, menopause-associated vasomotor symptoms, fibromyalgia, neuropathic pain, diabetic peripheral neuropathy (DPN), and chemotherapy-induced neuropathy. 
     
     
         65 . The method of  claim 59 , wherein the antidepressant causing sexual dysfunction is selected from an SSRI, an SNRI, a tricyclic antidepressant, and a tetracyclic anti-depressant. 
     
     
         66 . The method of  claim 59 , wherein a) the SSRI is selected from sertraline, citalopram, fluoxetine, escitalopram, paroxetine, fluvoxamine, duloxetine, venlafaxine, and desvenlafaxine; b) the SNRI is selected from duloxetine, venlafaxine, desvenlafaxine, milnacipran, and levomilnacipran; c) the tricyclic antidepressant is selected from clomipramine, trimipramine, amitriptyline, desipramine, imipramine, lofepramine, doxepin, nortriptyline, amoxapine, and protriptyline; and/or the tetracyclic antidepressant is selected from maprotiline and mirtazapine. 
     
     
         67 . The method of  claim 59 , wherein said topical composition is formulated as a lotion, an ointment, a cream, a suspension, a paste, a gel, a balm, a tincture, an emulsion, or a serum, any one of which is applied to the female genitalia. 
     
     
         68 . The method of  claim 59 , wherein the genital arousal area includes genitalia with absorptive mucosa, comprising one or more of: the introitus, the vulva, the labia minora, the clitoris and the vaginal vault. 
     
     
         69 . The method of  claim 59 , wherein the female sexual dysfunction is characterized by one or more of the following characteristics: difficulty achieving arousal and/or insufficient lubrication, difficulty in achieving and maintaining engorgement, and difficulty in achieving and maintaining lubrication. 
     
     
         70 . The method of  claim 58 , wherein the female sexual dysfunction is characterized by one or more of the following characteristics: difficulty in achieving orgasm, low orgasm intensity, or anorgasmia. 
     
     
         71 . The method of  claim 59 , wherein the female subject was previously treated with an anti-depressant that induced sexual dysfunction and the subject has persistent sexual dysfunction despite discontinuation of the antidepressant therapy. 
     
     
         72 . The method of  claim 59 , wherein the female subject is premenopausal. 
     
     
         73 . The method of  claim 59 , wherein the female subject is post-menopausal. 
     
     
         74 . The method as in  claim 59 , wherein the subject has been previously treated with, but did not satisfactorily respond to, one or more of the following treatments: (1) change of the time the antidepressant medication is taken, (2) drug holidays, (3) decrease the dose of the medication, (4) switching to or addition of mirtazapine, (5) switching to or addition of bupropion, (6) topical testosterone, (7) amantadine, (8) switching to or addition of trazodone, (9) methylphenidate, (10) behavioral therapy, and (11) acupuncture. 
     
     
         75 . The method as in  claim 59 , wherein the female subject is further treated with one or more of the following treatments: (1) change of the time the antidepressant medication is taken, (2) drug holidays, (3) decrease the dose of the medication, (4) switching to or addition of mirtazapine, (5) switching to or addition of bupropion, (6) topical testosterone, (7) acupuncture, (8) amantadine, (9) switching to or addition of trazodone, (10) methylphenidate, (11) behavioral therapy, and (12) dietary supplements. 
     
     
         76 . The method of  claim 59 , wherein the amelioration of the sexual dysfunction is exhibited by one or both of the following parameters:
 i) clitoral smooth muscle relaxation; and   ii) increased vaginal and clitoral blood flow.   
     
     
         77 . The method of  claim 59 , wherein the amelioration of the sexual dysfunction is exhibited by one or more of the following subjectively self-reported outcomes including:
 i) “increased lubrication/wetness during sexual activity”;   ii) “reaching orgasm more often”;   iii) “greater ease or achieving orgasm”;   iv) “being more satisfied”;   v) “higher level of sexual desire”; and   vi) “reduction in pain during sexual activity”.   
     
     
         78 . The method of  claim 59 , wherein the total amount of CBD applied is from 5 mg to 1,000 mg of CBD. 
     
     
         79 . The method of  claim 59 , wherein the composition is applied 1-60 min prior to sexual activity. 
     
     
         80 . The method of  claim 58 , wherein the CBD-containing composition is applied at 5-30 mins prior to the sexual activity. 
     
     
         81 . The method of  claim 58 , wherein CBD is hemp-derived and/or contains less than 0.3% THC by weight. 
     
     
         82 . The method of  claim 58 , wherein the concentration of CBD in the composition is from 1 mg/mL to 40 mg/mL. 
     
     
         83 . The method of  claim 58 , wherein the subject, upon having been treated with the CBD-containing composition for 3-6 months, reports arousal and or orgasmic improvements as measured by FSFI, wherein the improvement in sexual interest/arousal domain is by 1-2 points, and by 1-2 points in the orgasm domain of the FSFI. 
     
     
         84 . The method of claim  558 , wherein off-set time following the application of the CBD-containing composition is 0.5-5 hrs.