Inclusion Criteria:

1. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. 2. Aged 35-65 years old. 3. A female subject is eligible to participate if she is a) of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy, or postmenopausal defined as 12 months of spontaneous amenorrhea or b) of childbearing potential but not pregnant (as determined by urinary pregnancy test on screening and on each study day) and willing to use one of the contraception methods listed below. 4. Male subject must agree to use one of the contraception methods listed above. 5. Willing to abstain from alcohol for the duration of dosing. 6. Expanded Disability Status Scale (EDSS) >3.5 <6.5 (SPMS patients only)

Exclusion Criteria:

1. History of active neurological disease other than migraine or MS. 2. Clinically meaningful abnormalities in routine bloods including:

• - eGFR < 60ml/min.

• - Elevation of liver enzymes/bilirubin.

• - Prolonged prothrombin time.

• - Thrombocytopenia.

3. Use of the following medications or therapies:

• - Immunosuppressive or immunomodulatory drugs within the last 6 months.

• - Alemtuzumab or haematopeotic stem cell therapy.

• - Central nervous system depressants (including opioid analgesics, barbiturates, sleeping pills, antihistamines, antipsychotics) - P450 CY3A4 inducers or inhibitors.

• - oral contraceptives.

• - oral anticoagulants or antiplatelet agents other than low dose aspirin.

• - levothyroxine.

4. Currently breastfeeding. 5. Any clinical significant medical conditions that in the opinion of the investigator would compromise subjects' safety or compliance with study procedures. 6. History of any clinical condition which in the opinion of the principal investigator would compromise the scientific integrity of the study, such as some chronic systemic diseases affecting blood, liver or kidneys or endocrine system. 7. Unwillingness or inability to follow the procedures outlined in the protocol. 8. Subject is mentally or legally incapacitated. 9. Contraindication to XBD173 use: • Hypersensitivity to the active substance or to any of the excipients. 10. Contraindication to etifoxine use:

• - Myasthenia gravis.

- syndromes of glucose and galactose malabsorption or lactose deficiency

The 18 kiloDalton Translocator Protein (TSPO) is a mitochondrial protein highly expressed in myeloid cells. While the full range of its functions are unknown, preclinical and in vitro studies provide suggestive evidence that TSPO ligands alter TSPO protein function to bias monocytes/macrophages and microglia towards reparative phenotypes. XBD173 and etifoxine are two TSPO ligands and represent two distinct chemotypes. Etifoxine is a benzoxaine, licenced in France (although not the UK) for the treatment of anxiety. XBD173 (Emapunil) is a phenylpurine that has recently been investigated for the treatment of anxiety, but is not licensed. The aim of this experimental medicine study is to test the hypothesis in humans that functional changes effected by TSPO can induce pro-inflammatory monocytes/macrophages and microglia to adopt a reparative phenotype. People with multiple sclerosis (MS) will be enrolled in this study because monocytes from MS patients have a chronic pro-inflammatory phenotype. Healthy volunteers (HVs) will also be enrolled to determine whether TSPO mediated effects are immune state dependant. The primary objective of this study is to determine the effects of TSPO ligand binding on monocyte/macrophage phenotype in humans. The secondary objectives are: a To characterise immunological responses in blood plasma and in circulating immune cell subsets of healthy volunteers and people with SPMS after TSPO functional changes induced by challenge ligand binding. b To explore the potential dependence of these pharmacodynamic responses on variation at rs6971 (a common polymorphism influencing ligand binding affinities in the TSPO protein) in the TSPO gene.

Arms

Experimental: Etifoxine then XBD173

Experimental: XBD173 then Etifoxine

Interventions

Drug: - XBD173

7 days treatment

Drug: - Etifoxine

7 days treatment