CANNEFF preparation is a supportive therapeutic for women with gynecological problems. The primary indications for CANNEFF suppositories are based on two active ingredients: sodium hyaluronate and cannabidiol (CBD). Sodium hyaluronate assists the healing of vaginal and rectal mucosa as well as internal and external hemorrhoids; relieves pain, inflammation, irritation, swelling, and itching; may be recommended after treatment of vaginal inflammation or mycosis; promotes healing of postpartum trauma; and promotes wound healing after surgery and radiation therapy. It can be used to relieve symptoms of vaginal dryness and discomfort due to estrogen deficiency. Another active substance is cannabidiol, which in combination with sodium hyaluronate brings greater therapeutic possibilities supported by evidence from randomized clinical trials. The pharmacological effects of CBD are described below.

Anti-inflammatory Effect

Preparations containing hyaluronic acid or its salts and derivatives have long been used to promote healing, restore hydration, and reduce inflammation of the skin and mucous membranes [1]. The anti-inflammatory and cytoprotective (antioxidant) effects of CBD have been demonstrated. CBD both directly and indirectly affects the endocannabinoid system (ECS), which plays a key role in maintaining a stable internal environment. CBD assists in capturing reactive oxygen species [2a] and generally helps maintain redox homeostasis [2b], which is directly related to the modulation of inflammatory processes. Improvements in experimentally induced colitis [3a] and collagen-induced arthritis and reductions in the severity of neuro-inflammation and encephalomyelitis [3b] have been observed following administration of CBD. The anti-inflammatory effect of CBD is its primary pharmacological effect.

Reduction of Pain and Discomfort

CBD interacts with a range of cellular receptors, including receptor systems related to the perception of pain [4]. The analgesic effect of CBD has been demonstrated in animal models, and CBD has been shown to be very well tolerated. In a pilot study involving patients with inflammatory skin diseases, all participants reported a reduction of pain and itching and an overall improvement in skin condition following administration of transdermal CBD gel [5]. In a case study involving patients suffering from the inflammatory skin disease epidermolysis bullosa, all participants described faster healing, reduced blistering, and decreased pain resulting from the disease [6]. Because they restore mucosal hydration, preparations containing hyaluronate are also effective in reducing the symptoms of vaginal dryness and are recommended for reducing pain during intercourse and other problems associated with hormonal imbalance [7]. In combining sodium hyaluronate with CBD-mediated analgesia and anti-inflammatory effects, CANNEFF Vag Sup vaginal suppositories may be a suitable replacement for hormonal preparations that reduce vaginal discomfort due to estrogen deficiency related to premenstrual syndrome or menopause.

Anxiolytic Effect and Improvement of Sleep

Preclinical trials have shown a positive effect of CBD on the suppression of anxiety, stress, and panic in experimental animals. CBD acts as a regulator of certain receptors of the peripheral nervous system responsible for regulating fear and anxiety [8]. Clinical testing in healthy volunteers and individuals with anxiety disorders indicates potential use of CBD as an anxiolytic suitable for reducing the severity of general anxiety, panic, social anxiety, obsessive-compulsive disorder, and post-traumatic disorder [9].

In a pilot study, volunteers reported a subjectively lower degree of anxiety after oral administration of 400 mg of CBD. This was supported by demonstrably altered brain activity in centers that process anxiety [10]. In a clinical study of the effect of CBD on patients with social anxiety disorder, participants received a single oral dose of 600 mg of CBD before a simulated public speaking test. Compared to the placebo group, the CBD test group showed significantly lower manifestations of anxiety, fewer problems in their speech, and a lower level of discomfort, comparable to the control group of individuals not suffering from social anxiety [11].

As anxiety disorders are often associated with sleep disorders, CBD is recommended as a supportive therapeutic for sleep disturbances. In the majority of cases, administration of CBD is well tolerated by patients. The effect of CBD on anxiety and sleep quality was tested in a clinical study of 72 adult subjects, the majority of whom received 25 mg of CBD daily in the form of an oral capsule. Within the first month, anxiety scores improved for 57 subjects (79.2%), and sleep scores improved for 48 subjects (66.7%) [12].

A Non-hormonal Alternative to Hormonal Imbalance Treatments

CANNEFF Vag Sup vaginal suppositories can be used as a complementary treatment for minor injuries or discomfort in the vaginal area. A positive effect of sodium hyaluronate on post-menopausal vaginal atrophy, vaginal dryness, and similar symptoms has been reported. Topical administration of preparations containing hyaluronate in clinical trials has provided distinct relief from itching, pain, and dryness of the vaginal mucosa [7, 13]. Preparations containing sodium hyaluronate have shown effects comparable to estrogen-based hormonal preparations [14].

Summary

CANNEFF Vag Sup vaginal suppositories can be a non-hormonal alternative to treatments for suppressing mood swings, pain, and discomfort associated with premenstrual syndrome and menopause.

References

[1]         V. Voinchet, P. Vasseur, J. Kern, Efficacy and safety of hyaluronic acid in the management of acute wounds. Am. J. Clin. Dermatol., 2006, 7, 353-357.

[2]         a) S. Atalay, I. Jarocka-Karpowicz, E. Skrzydlewska, Antioxidative and Anti-Inflammatory Properties of Cannabidiol. Antioxidants (Basel), 2019, 9, 21. b) J. Vacek, J. Storch, et al. Antioxidant function of phytocannabinoids: molecular basis of their stability and cytoprotective properties under UV-irradiation. Free Radic. Biol. Med. 2021, 164, 258-270.

[3]         a) R. Schicho, M. Storr, Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis in mice. Pharmacology, 2012, 89, 149-155. b) S. Burstein, Cannabidiol (CBD) and its analogs: a review of their effects on inflammation. Bioorg. Med. Chem. 2015, 23, 1377 – 1385.

[4]         J. Mlost, M. Bryk, K. Starowicz, Cannabidiol for Pain Treatment: Focus on Pharmacology and Mechanism of Action. Int. J. Mol. Sci., 2020, 21, 8870.

[5]         B. Palmieri, C. Laurino, M. Vadalà, A therapeutic effect of cbd-enriched ointment in inflammatory skin diseases and cutaneous scars. Clin. Ter., 2019, 170, e93-e99.

[6]         M. P. Chelliah, Z. Zinn, P. Khuu, J.M.C. Teng, Self-initiated use of topical cannabidiol oil for epidermolysis bullosa. Pediatr. Dermato.l, 2018, 35, e224-e227.

[7]         A. Jokar, T. Davari, N. Asadi, F. Ahmadi, S. Foruhari, Comparison of the Hyaluronic Acid Vaginal Cream and Conjugated Estrogen Used in Treatment of Vaginal Atrophy of Menopause Women: A Randomized Controlled Clinical Trial. Int. J. Community Based Nurs.. Midwifery, 2016, 4, 69-78.

[8]         E.M. Blessing, M.M. Steenkamp, J. Manzanares, C.R. Marmar, Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics, 2015, 12, 825-836.

[9]         M. Wright, P. Di Ciano, B. Brands, Use of Cannabidiol for the Treatment of Anxiety: A Short Synthesis of Pre-Clinical and Clinical Evidence. Cannabis Cannabinoid Res.., 2020, 5, 191-196.

[10]       J.A. Crippa, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J. Psychopharmacol., 2011, 25, 121-130.

[11]       J.A. Crippa, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology, 2011, 36, 1219-1226.

[12]       S. Shannon, N. Lewis, H. Lee, S. Hughes, Cannabidiol in Anxiety and Sleep: A Large Case Series. Perm. J., 2019, 23, 18-41.

[13]       M. Origoni, et al. Postmenopausal vulvovaginal atrophy (VVA) is positively improved by topical hyaluronic acid application. A prospective, observational study. Eur. Rev. Med. Pharmacol. Sci., 2016, 20, 4190-4195.

[14]       J. Chen, L. Geng, X. Song, H. Li, N. Giordan, Q. Liao, Evaluation of the efficacy and safety of hyaluronic acid vaginal gel to ease vaginal dryness: a multicenter, randomized, controlled, open-label, parallel-group, clinical trial. J. Sex. Med., 2013, 10, 1575-1584.

Anti-inflammatory Effect

This two-component medical product containing sodium hyaluronate and cannabidiol is intended to restore hydration and reduce inflammation of the intestinal mucosa [1]. Sodium hyaluronate aids in the healing of the rectal mucosa and internal and external hemorrhoids, reduces pain, inflammation, irritation, swelling, and itching, and may be recommended to promote wound healing after surgery or radiation therapy.

CBD both directly and indirectly affects the endocannabinoid system (ECS), which plays a key role in maintaining a stable internal environment. CBD assists in capturing reactive oxygen species [2a] and generally helps maintain redox homeostasis [2b], which is directly related to the modulation of inflammatory processes. Improvements in experimentally induced colitis [3a] and collagen-induced arthritis and reductions in the severity of neuro-inflammation and encephalomyelitis [3b] have been observed following administration of CBD. The anti-inflammatory effect of CBD is its primary pharmacological effect.

CBD has been discussed as an ideal candidate for reducing idiopathic intestinal inflammation, i.e. Crohn’s disease and ulcerative colitis [4]. CBD use for these indications is very well tolerated [5]. The effect of CBD on Crohn’s disease was tested in a clinical study in 20 patients. Oral administration of 20 mg of CBD daily was very well tolerated [6]. A bioavailability of 6% has been reported for oral administration, and a pharmacological effect is achieved with an orally administered dose of 100 mg. Long-term use of medical cannabis in 127 patients with inflammatory diseases of the gastrointestinal system led to a significant improvement of symptoms in the majority of participants and to a reduction in the use of other drugs such as steroids. Patients in the experiment used cannabis with an average dose of 170 mg of CBD per day, mostly by inhalation [7]. Considering the results of preclinical testing of the anti-inflammatory effects of CBD, it has the potential to alleviate symptoms of gastrointestinal mucositis. A combination of sodium hyaluronate and CBD can therefore have a supportive therapeutic effect and reduce symptoms associated with idiopathic intestinal inflammation.

Reduction of Pain, Itching, and Swelling

CBD acts as a regulator of certain receptors of the peripheral nervous system responsible for regulating fear and anxiety [8]. CBD is a non-addictive alternative to opioid use [9]. In a clinical study of 20 patients with inflammatory skin diseases, all participants reported a reduction in pain, relief from itching, and an overall improvement in skin condition following administration of transdermal CBD gel [10]. In a case study involving patients suffering from the inflammatory skin disease epidermolysis bullosa, all participants described faster healing, reduced blistering, and decreased pain resulting from the disease [11]. Given the combination of analgesia and anti-inflammatory effects, CBD preparations may be generally suitable for alleviating unpleasant symptoms and pain associated with various injuries. CANNEFF Sup rectal suppositories are indicated for minor injuries in the rectal area, such as cracks, fissures, lesions, or hemorrhoids associated with a sedentary lifestyle.

Anxiolytic Effect and Improvement of Sleep

Preclinical trials have shown a positive effect of CBD on the suppression of anxiety, stress, and panic in experimental animals. CBD acts as a regulator of certain receptors of the peripheral nervous system responsible for regulating fear and anxiety [12]. Clinical testing in healthy volunteers and individuals with anxiety disorders also indicates potential use of CBD as an anxiolytic in cases of various disorders: general anxiety, panic, social anxiety, obsessive-compulsive, and post-traumatic [13].

In a pilot study, volunteers reported a subjectively lower degree of anxiety after oral administration of 400 mg of CBD. This was supported by demonstrably altered brain activity in centers that process anxiety [14]. In a clinical study of the effect of CBD on patients with social anxiety disorder, participants received a single oral dose of 600 mg of CBD before a simulated public speaking test. Compared to the placebo group, the CBD test group showed significantly lower manifestations of anxiety, fewer problems in their speech, and a lower level of discomfort, comparable to the control group of individuals not suffering from social anxiety [15].

As anxiety disorders are often associated with sleep disorders, CBD is recommended as a supportive therapeutic for sleep disturbances. In the majority of cases, administration of CBD is well tolerated by patients. The effect of CBD on anxiety and sleep quality was tested in a clinical study of 72 adult subjects, the majority of whom received 25 mg of CBD daily in the form of an oral capsule. Within the first month, anxiety scores improved for 57 subjects (79.2%), and sleep scores improved for 48 subjects (66.7%) [16].

Summary

CANNEFF Sup rectal suppositories are a supportive therapeutic agent suitable for relieving inflammation and pain in the rectal area, reducing bodily and psychological discomfort. The preparation is also suitable for helping with symptoms associated with idiopathic intestinal inflammation.

References

[1]         V. Liguori, C. Guillemin, G. F. Pesce, R. O. Mirimanoff, J. Bernier, Double-blind, randomized clinical study comparing hyaluronic acid cream to placebo in patients treated with radiotherapy. Radiother. Oncol., 1997, 42, 155-161.

[2]         a) S. Atalay, I. Jarocka-Karpowicz, E. Skrzydlewska, Antioxidative and Anti-Inflammatory Properties of Cannabidiol. Antioxidants (Basel), 2019, 9, 21. b) J. Vacek, J. Storch, et al. Antioxidant function of phytocannabinoids: molecular basis of their stability and cytoprotective properties under UV-irradiation. Free Radic. Biol. Med. 2021, 164, 258-270.

[3]         a) R. Schicho, M. Storr, Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis in mice. Pharmacology, 2012, 89, 149-155. b) S. Burstein, Cannabidiol (CBD) and its analogs: a review of their effects on inflammation. Bioorg. Med. Chem. 2015, 23, 1377 – 1385.

[4]         G. Esposito, D. D. Filippis, C. Cirillo, T. Iuvone, E. Capoccia, C. Scuderi, A. Steardo, R. Cuomo, L. Steardo, Cannabidiol in inflammatory bowel diseases: a brief overview. Phytother. Res., 2013, 27, 633-636.

[5]         C. Larsen, J. Shahinas, J., Dosage, Efficacy and Safety of Cannabidiol Administration in Adults: A Systematic Review of Human Trials. J. Clin. Med. Res., 2020, 12, 129-141.

[6]         T. Naftali, R. Mechulam, A. Marii, G. Gabay, A. Stein, M. Bronshtain, I. Laish, F. Benjaminov, F. M. Konikoff, Low-Dose Cannabidiol Is Safe but Not Effective in the Treatment for Crohn’s Disease, a Randomized Controlled Trial. Dig. Dis. Sci., 2017, 62, 1615-1620.

[7]         T. Naftali, L. Bar-Lev Schleider, F. Sklerovsky Benjaminov, I. Lish, F. M. Konikoff, Y. Ringel, Medical cannabis for inflammatory bowel disease: real-life experience of mode of consumption and assessment of side-effects. Eur. J. Gastroenterol. Hepatol., 2019, 31, 1376-1381.

[8]         J. Mlost, M. Bryk, K. Starowicz, Cannabidiol for Pain Treatment: Focus on Pharmacology and Mechanism of Action. Int. J. Mol. Sci., 2020, 21, 8870.

[9]         J. P. Eskander, J. Spall, A. Spall, R. V. Shah, A. D. Kaye, Cannabidiol (CBD) as a treatment of acute and chronic back pain: A case series and literature review. J. Opioid. Manag., 2020, 16, 215-218.

[10]       B. Palmieri, C. Laurino, M. Vadalà, A therapeutic effect of cbd-enriched ointment in inflammatory skin diseases and cutaneous scars. Clin. Ter., 2019, 170, 93-99.

[11]       M. P. Chelliah, Z. Zinn, P. Khuu, J. M. C. Teng, Self-initiated use of topical cannabidiol oil for epidermolysis bullosa. Pediatr. Dermatol., 2018, 35, 224-227.

[12]       E. M. Blessing, M. M. Steenkamp, J. Manzanares, C. R. Marmar, Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics, 2015, 12, 825-836.

[13]       M. Wright, P. Di Ciano, B. Brands, Use of Cannabidiol for the Treatment of Anxiety: A Short Synthesis of Pre-Clinical and Clinical Evidence. Cannabis Cannabinoid Res., 2020, 5, 191-196.

[14]       J.A Crippa, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J. Psychopharmacol., 2011, 25, 121-130.

[15]       J.A. Crippa, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology, 2011, 36, 1219-1226.

[16]       S. Shannon, N. Lewis, H. Lee, S. Hughes, Cannabidiol in Anxiety and Sleep: A Large Case Series. Perm. J., 2019, 23, 18-41.